About this Journal Submit a Manuscript Table of Contents
Prostate Cancer
Volume 2013 (2013), Article ID 920612, 23 pages
http://dx.doi.org/10.1155/2013/920612
Review Article

Dissecting Major Signaling Pathways throughout the Development of Prostate Cancer

1Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Avenida Prof. Lineu Prestes 1730, 05508-900 São Paulo, SP, Brazil
2Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Avenida Prof. Lineu Prestes 580, 05508-000 São Paulo, SP, Brazil
3Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, Rua do Matão 277, 05508-900 São Paulo, SP, Brazil
4Instituto Israelita de Ensino e Pesquisa Albert Einstein, Avenida Albert Einstein 627/701, 05652-000 São Paulo, SP, Brazil
5International Center for Genetic Engineering & Biotechnology (ICGEB), Cancer Genomics Group and Division of Medical Biochemistry, University of Cape Town, Cape Town 7925, South Africa
6Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA

Received 30 November 2012; Revised 25 March 2013; Accepted 28 March 2013

Academic Editor: Craig Robson

Copyright © 2013 Henrique B. da Silva et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. Verras and Z. Sun, “Roles and regulation of Wnt signaling and β-catenin in prostate cancer,” Cancer Letters, vol. 237, no. 1, pp. 22–32, 2006. View at Publisher · View at Google Scholar · View at Scopus
  2. J. K. Mullins and S. Loeb, “Environmental exposures and prostate cancer,” Urologic Oncology, vol. 30, pp. 216–219, 2012.
  3. R. Siegel, C. DeSantis, K. Virgo et al., “Cancer treatment and survivorship statistics, 2012,” CA: A Cancer Journal for Clinicians, vol. 62, pp. 220–241, 2012.
  4. F. C. Maluf, O. Smaletz, and D. Herchenhorn, “Castration-resistant prostate cancer: systemic therapy in 2012,” Clinics, vol. 67, pp. 389–394, 2012.
  5. M. M. Center, A. Jemal, J. Lortet-Tieulent et al., “International variation in prostate cancer incidence and mortality rates,” European Urology, vol. 61, pp. 1079–1092, 2012.
  6. G. Arcangeli, B. Saracino, S. Gomellini et al., “A Prospective phase III randomized trial of hypofractionation versus conventional fractionation in patients with high-risk prostate cancer,” International Journal of Radiation Oncology Biology Physics, vol. 78, no. 1, pp. 11–18, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. H. G. Sim and C. W. S. Cheng, “Changing demography of prostate cancer in Asia,” European Journal of Cancer, vol. 41, no. 6, pp. 834–845, 2005. View at Publisher · View at Google Scholar · View at Scopus
  8. S. H. Reuben, “Reducing environmental cancer risk: what we can do now,” The President's Cancer Panel, pp. 1–240, 2010.
  9. M. F. Leitzmann and S. Rohrmann, “Risk factors for the onset of prostatic cancer: age, location, and behavioral correlates,” Clinical Epidemiology, vol. 4, pp. 1–11, 2012.
  10. B. G. Timms, “Prostate development: a historical perspective,” Differentiation, vol. 76, no. 6, pp. 565–577, 2008. View at Publisher · View at Google Scholar · View at Scopus
  11. A. R. Kristal, K. B. Arnold, M. L. Neuhouser et al., “Diet, supplement use, and prostate cancer risk: results from the prostate cancer prevention trial,” American Journal of Epidemiology, vol. 172, no. 5, pp. 566–577, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. L. J. Su, L. Arab, S. E. Steck et al., “Obesity and prostate cancer aggressiveness among African and Caucasian Americans in a population-based study,” Cancer Epidemiology Biomarkers and Prevention, vol. 20, no. 5, pp. 844–853, 2011. View at Publisher · View at Google Scholar · View at Scopus
  13. S. Koifman and R. J. Koifman, “Environment and cancer in Brazil: an overview from a public health perspective,” Mutation Research, vol. 544, no. 2-3, pp. 305–311, 2003. View at Publisher · View at Google Scholar · View at Scopus
  14. R. Sichieri, J. E. Everhart, and G. A. Mendonca, “Diet and mortality from common cancers in Brazil: an ecological study,” Cadernos de Saúde Pública, vol. 12, pp. 53–59, 1996.
  15. P. Cocco, “On the rumors about the silent spring. Review of the scientific evidence linking occupational and environmental pesticide exposure to endocrine disruption health effects,” Cadernos de Saúde Pública, vol. 18, no. 2, pp. 379–402, 2002. View at Scopus
  16. H. J. van der Rhee, E. de Vries, and J. W. W. Coebergh, “Does sunlight prevent cancer? A systematic review,” European Journal of Cancer, vol. 42, no. 14, pp. 2222–2232, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. S. J. Freedland, W. B. Isaacs, E. A. Platz et al., “Prostate size and risk of high-grade, advanced prostate cancer and biochemical progression after radical prostatectomy: a search database study,” Journal of Clinical Oncology, vol. 23, no. 30, pp. 7546–7554, 2005. View at Publisher · View at Google Scholar · View at Scopus
  18. H. T. Lynch and J. F. Lynch, “The Lynch syndrome: melding natural history and molecular genetics to genetic counseling and cancer control,” Cancer Control, vol. 3, no. 1, pp. 13–19, 1996. View at Scopus
  19. J. K. Jin, F. Dayyani, and G. E. Gallick, “Steps in prostate cancer progression that lead to bone metastasis,” International Journal of Cancer, vol. 128, no. 11, pp. 2545–2561, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. P. E. Lonergan and D. J. Tindall, “Androgen receptor signaling in prostate cancer development and progression,” Journal of Carcinogenesis, vol. 10, article 20, 2011.
  21. S. A. Boorjian, J. A. Eastham, M. Graefen et al., “A critical analysis of the long-term impact of radical prostatectomy on cancer control and function outcomes,” European Urology, vol. 61, pp. 664–675, 2012.
  22. Z. Culig, A. Hobisch, M. V. Cronauer et al., “Androgen receptor activation in prostatic tumor cell lines by insulin- like growth factor-I, keratinocyte growth factor, and epidermal growth factor,” Cancer Research, vol. 54, no. 20, pp. 5474–5478, 1994. View at Scopus
  23. A. Wolk, C. S. Mantzoros, S. O. Andersson et al., “Insulin-like growth factor 1 and prostate cancer risk: a population-based, case-control study,” Journal of the National Cancer Institute, vol. 90, no. 12, pp. 911–915, 1998. View at Scopus
  24. D. Gioeli, S. B. Ficarro, J. J. Kwiek et al., “Androgen receptor phosphorylation. Regulation and identification of the phosphorylation sites,” Journal of Biological Chemistry, vol. 277, no. 32, pp. 29304–29314, 2002. View at Scopus
  25. Z. Guo, B. Dai, T. Jiang et al., “Regulation of androgen receptor activity by tyrosine phosphorylation,” Cancer Cell, vol. 10, no. 4, pp. 309–319, 2006. View at Publisher · View at Google Scholar · View at Scopus
  26. E. Hernes, Fosså, A. Berner, B. Otnes, and J. M. Nesland, “Expression of the epidermal growth factor receptor family in prostate carcinoma before and during androgen-independence,” British Journal of Cancer, vol. 90, no. 2, pp. 449–454, 2004. View at Publisher · View at Google Scholar · View at Scopus
  27. S. M. Green, E. A. Mostaghel, and P. S. Nelson, “Androgen action and metabolism in prostate cancer,” Molecular and Cellular Endocrinology, vol. 360, pp. 3–13, 2012.
  28. S. Q. Yu, K. P. Lai, S. J. Xia, H. C. Chang, C. Chang, and S. Yeh, “The diverse and contrasting effects of using human prostate cancer cell lines to study androgen receptor roles in prostate cancer,” Asian Journal of Andrology, vol. 11, no. 1, pp. 39–48, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. C. GIampietri, S. Petrungaro, F. Padula et al., “Autophagy modulators sensitize prostate epithelial cancer cell lines to TNF-alpha-dependent apoptosis,” Apoptosis, vol. 17, no. 11, pp. 1210–1222, 2012.
  30. X. Huang, F. Yuan, M. Liang et al., “M-HIFU inhibits tumor growth, suppresses STAT3 activity and enhances tumor specific immunity in a transplant tumor model of prostate cancer,” PLoS ONE, vol. 7, Article ID e41632, 2012.
  31. A. Vajda, L. Marignol, C. Barrett et al., “Gene expression analysis in prostate cancer: the importance of the endogenous control,” Prostate, vol. 73, pp. 382–390, 2012.
  32. C. E. Lin, S. U. Chen, C. C. Lin et al., “Lysophosphatidic acid enhances vascular endothelial growth factor-C expression in human prostate cancer PC-3 cells,” PLoS ONE, vol. 7, Article ID e41096, 2012.
  33. P. Saraon, N. Musrap, D. Cretu et al., “Proteomic profiling of androgen-independent prostate cancer cell lines reveals a role for protein S during the development of high grade and castration-resistant prostate cancer,” Journal of Biological Chemistry, vol. 287, pp. 34019–34031, 2012.
  34. B. S. Carver, C. Chapinski, J. Wongvipat et al., “Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer,” Cancer Cell, vol. 19, no. 5, pp. 575–586, 2011. View at Publisher · View at Google Scholar · View at Scopus
  35. J. A. Ewald, J. A. Desotelle, D. R. Church et al., “Androgen deprivation induces senescence characteristics in prostate cancer cells in vitro and in vivo,” Prostate, vol. 73, pp. 337–345, 2012.
  36. P. J. Maxwell, J. Coulter, S. M. Walker et al., “Potentiation of inflammatory CXCL8 signalling sustains cell survival in PTEN-deficient prostate carcinoma,” European Urology, 2012.
  37. R. S. Jackson II, W. Placzek, A. Fernandez et al., “Sabutoclax, a Mcl-1 antagonist, inhibits tumorigenesis in transgenic mouse and human xenograft models of prostate cancer,” Neoplasia, vol. 14, pp. 656–665, 2012.
  38. H. Wang, Y. Xu, Z. Fang, S. Chen, S. P. Balk, and X. Yuan, “Doxycycline regulated induction of AKT in murine prostate drives proliferation independently of p27 cyclin dependent kinase inhibitor downregulation,” PLoS ONE, vol. 7, Article ID e41330, 2012.
  39. M. A. Reynolds, “Molecular alterations in prostate cancer,” Cancer Letters, vol. 271, no. 1, pp. 13–24, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. M. E. Grossmann, H. Huang, and D. J. Tindall, “Androgen receptor signaling in androgen-refractory prostate cancer,” Journal of the National Cancer Institute, vol. 93, no. 22, pp. 1687–1697, 2001. View at Scopus
  41. S. C. Chan, Y. Li, and S. M. Dehm, “Androgen receptor splice variants activate androgen receptor target genes and support aberrant prostate cancer cell growth independent of canonical androgen receptor nuclear localization signal,” Journal of Biological Chemistry, vol. 287, pp. 19736–19749, 2012.
  42. G. Castoria, L. D'Amato, A. Ciociola et al., “Androgen-induced cell migration: role of androgen receptor/filamin A association,” PLoS ONE, vol. 6, Article ID e17218, 2012.
  43. K. K. Waltering, A. Urbanucci, and T. Visakorpi, “Androgen receptor (AR) aberrations in castration-resistant prostate cancer,” Molecular and Cellular Endocrinology, vol. 360, pp. 38–43, 2012.
  44. H. Wang, C. Zhang, A. Rorick et al., “CCI-779 inhibits cell-cycle G2-M progression and invasion of castration-resistant prostate cancer via attenuation of UBE2C transcription and mRNA stability,” Cancer Research, vol. 71, no. 14, pp. 4866–4876, 2011. View at Publisher · View at Google Scholar · View at Scopus
  45. A. Urbanucci, B. Sahu, J. Seppala et al., “Overexpression of androgen receptor enhances the binding of the receptor to the chromatin in prostate cancer,” Oncogene, vol. 31, pp. 2153–2163, 2012.
  46. M. Shiota, A. Yokomizo, and S. Naito, “Increased androgen receptor transcription: a cause of castration-resistant prostate cancer and a possible therapeutic target,” Journal of Molecular Endocrinology, vol. 47, no. 1, pp. R25–R41, 2011. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Shiota, A. Yokomizo, and S. Naito, “Oxidative stress and androgen receptor signaling in the development and progression of castration-resistant prostate cancer,” Free Radical Biology and Medicine, vol. 51, pp. 1320–1328, 2011.
  48. Y. Zuo and J. K. Cheng, “Small ubiquitin-like modifier protein-specific protease 1 and prostate cancer,” Asian Journal of Andrology, vol. 11, no. 1, pp. 36–38, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. T. Bawa-Khalfe, J. Cheng, Z. Wang, and E. T. H. Yeh, “Induction of the SUMO-specific protease 1 transcription by the androgen receptor in prostate cancer cells,” Journal of Biological Chemistry, vol. 282, no. 52, pp. 37341–37349, 2007. View at Publisher · View at Google Scholar · View at Scopus
  50. N. D. Perkins, “Integrating cell-signalling pathways with NF-kappaB and IKK function,” Nature Reviews Molecular Cell Biology, vol. 8, pp. 49–62, 2007.
  51. C. Cai, F. N. Jiang, Y. X. Liang et al., “Classical and alternative nuclear factor-kappaB pathways: a comparison among normal prostate, benign prostate hyperplasia and prostate cancer,” Pathology and Oncology Research, vol. 17, pp. 873–878, 2011.
  52. V. Tergaonkar, “NFκB pathway: a good signaling paradigm and therapeutic target,” International Journal of Biochemistry and Cell Biology, vol. 38, no. 10, pp. 1647–1653, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. B. Razani, A. D. Reichardt, and G. Cheng, “Non-canonical NF-kappaB signaling activation and regulation: principles and perspectives,” Immunological Reviews, vol. 244, pp. 44–54, 2011.
  54. R. C. Rickert, J. Jellusova, and A. V. Miletic, “Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease,” Immunological Reviews, vol. 244, pp. 115–133, 2011.
  55. L. Gu, A. Dagvadorj, J. Lutz et al., “Transcription factor Stat3 stimulates metastatic behavior of human prostate cancer cells in vivo, whereas Stat5b has a preferential role in the promotion of prostate cancer cell viability and tumor growth,” American Journal of Pathology, vol. 176, no. 4, pp. 1959–1972, 2010. View at Publisher · View at Google Scholar · View at Scopus
  56. J. Chen, K. V. Giridhar, L. Zhang, S. Xu, and Q. Jane Wang, “A protein kinase C/protein kinase D pathway protects LNCaP prostate cancer cells from phorbol ester-induced apoptosis by promoting ERK1/2 and NF-κB activities,” Carcinogenesis, vol. 32, no. 8, pp. 1198–1206, 2011. View at Publisher · View at Google Scholar · View at Scopus
  57. A. Hsu, R. S. Bruno, C. V. Löhr et al., “Dietary soy and tea mitigate chronic inflammation and prostate cancer via NFκB pathway in the Noble rat model,” Journal of Nutritional Biochemistry, vol. 22, no. 5, pp. 502–510, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. R. Benelli, R. Vene, M. Ciarlo, S. Carlone, O. Barbieri, and N. Ferrari, “The AKT/NF-kappaB inhibitor xanthohumol is a potent anti-lymphocytic leukemia drug overcoming chemoresistance and cell infiltration,” Biochemical Pharmacology, vol. 83, pp. 1634–1642, 2012.
  59. G. Jain, C. Voogdt, A. Tobias et al., “IkappaB kinases modulate the activity of the androgen receptor in prostate carcinoma cell lines,” Neoplasia, vol. 14, pp. 178–189, 2012.
  60. Y. Fang, H. Sun, J. Zhai et al., “Antitumor activity of NF-kB decoy oligodeoxynucleotides in a prostate cancer cell line,” Asian Pacific Journal of Cancer Prevention, vol. 12, pp. 2721–2726, 2012.
  61. W. Xiao, D. R. Hodge, L. Wang, X. Yang, X. Zhang, and W. L. Farrar, “Co-operative functions between nuclear factors NFκB and CCAT/enhancer-binding protein-β (C/EBP-β) regulate the IL-6 promoter in autocrine human prostate cancer cells,” Prostate, vol. 61, no. 4, pp. 354–370, 2004. View at Publisher · View at Google Scholar · View at Scopus
  62. S. Shukla, G. T. MacLennan, P. Fu et al., “Nuclear factor-κB/p65 (Rel A) is constitutively activated in human prostate adenocarcinoma and correlates with disease progression,” Neoplasia, vol. 6, no. 4, pp. 390–400, 2004. View at Publisher · View at Google Scholar · View at Scopus
  63. C. D. Chen and C. L. Sawyers, “NF-κB activates prostate-specific antigen expression and is upregulated in androgen-independent prostate cancer,” Molecular and Cellular Biology, vol. 22, no. 8, pp. 2862–2870, 2002. View at Publisher · View at Google Scholar · View at Scopus
  64. M. Paz De Miguel, M. Royuela, F. R. Bethencourt, L. Santamaría, B. Fraile, and R. Paniagua, “Immunoexpression of tumour necrosis factor-α and its receptors 1 and 2 correlates with proliferation/apoptosis equilibrium in normal, hyperplasic and carcinomatous human prostrate,” Cytokine, vol. 12, no. 5, pp. 535–538, 2000. View at Publisher · View at Google Scholar · View at Scopus
  65. G. Rodriguez-Berriguete, B. Fraile, R. Paniagua, P. Aller, and M. Royuela, “Expression of NF-kappaB-related proteins and their modulation during TNF-alpha-provoked apoptosis in prostate cancer cells,” Prostate, vol. 72, pp. 40–50, 2012.
  66. Y. Bouraoui, M. Ricote, I. García-Tuñón et al., “Pro-inflammatory cytokines and prostate-specific antigen in hyperplasia and human prostate cancer,” Cancer Detection and Prevention, vol. 32, no. 1, pp. 23–32, 2008. View at Publisher · View at Google Scholar · View at Scopus
  67. S. Srinivasan, R. Kumar, S. Koduru, A. Chandramouli, and C. Damodaran, “Inhibiting TNF-mediated signaling: a novel therapeutic paradigm for androgen independent prostate cancer,” Apoptosis, vol. 15, no. 2, pp. 153–161, 2010. View at Publisher · View at Google Scholar · View at Scopus
  68. G. Rodríguez-Berriguete, B. Fraile, F. R. de Bethencourt et al., “Role of IAPs in prostate cancer progression: immunohistochemical study in normal and pathological (benign hyperplastic, prostatic intraepithelial neoplasia and cancer) human prostate,” BMC Cancer, vol. 10, article 18, 2010. View at Publisher · View at Google Scholar · View at Scopus
  69. C. D. Chen, D. S. Welsbie, C. Tran et al., “Molecular determinants of resistance to antiandrogen therapy,” Nature Medicine, vol. 10, no. 1, pp. 33–39, 2004. View at Publisher · View at Google Scholar · View at Scopus
  70. L. Zhang, S. Altuwaijri, F. Deng et al., “NF-κB regulates androgen receptor expression and prostate cancer growth,” American Journal of Pathology, vol. 175, no. 2, pp. 489–499, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. G. Jain, M. V. Cronauer, M. Schrader, P. Moller, and R. B. Marienfeld, “NF-kappaB signaling in prostate cancer: a promising therapeutic target?” World Journal of Urology, vol. 30, pp. 303–310, 2012.
  72. S. I. Grivennikov and M. Karin, “Dangerous liaisons: STAT3 and NF-κB collaboration and crosstalk in cancer,” Cytokine and Growth Factor Reviews, vol. 21, no. 1, pp. 11–19, 2010. View at Publisher · View at Google Scholar · View at Scopus
  73. G. Schneider and O. H. Kramer, “NFkappaB/p53 crosstalk-a promising new therapeutic target,” Biochimica et Biophysica Acta, vol. 1815, pp. 90–103, 2011.
  74. A. Oeckinghaus, M. S. Hayden, and S. Ghosh, “Crosstalk in NF-kappaB signaling pathways,” Nature Immunology, vol. 12, pp. 695–708, 2011.
  75. I. Vivanco and C. L. Sawyers, “The phosphatidylinositol 3-kinase-AKT pathway in human cancer,” Nature Reviews Cancer, vol. 2, no. 7, pp. 489–501, 2002. View at Scopus
  76. A. G. Bader, S. Kang, L. Zhao, and P. K. Vogt, “Oncogenic PI3K deregulates transcription and translation,” Nature Reviews Cancer, vol. 5, no. 12, pp. 921–929, 2005. View at Publisher · View at Google Scholar · View at Scopus
  77. J. A. Engelman, J. Luo, and L. C. Cantley, “The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism,” Nature Reviews Genetics, vol. 7, no. 8, pp. 606–619, 2006. View at Publisher · View at Google Scholar · View at Scopus
  78. D. A. Guertin and D. M. Sabatini, “Defining the role of mTOR in cancer,” Cancer Cell, vol. 12, no. 1, pp. 9–22, 2007. View at Publisher · View at Google Scholar · View at Scopus
  79. L. Bozulic and B. A. Hemmings, “PIKKing on PKB: regulation of PKB activity by phosphorylation,” Current Opinion in Cell Biology, vol. 21, no. 2, pp. 256–261, 2009. View at Publisher · View at Google Scholar · View at Scopus
  80. M. P. Scheid and J. R. Woodgett, “PKB/AKT: functional insights from genetic models,” Nature Reviews Molecular Cell Biology, vol. 2, no. 10, pp. 760–768, 2001. View at Publisher · View at Google Scholar · View at Scopus
  81. B. D. Manning and L. C. Cantley, “AKT/PKB signaling: navigating downstream,” Cell, vol. 129, no. 7, pp. 1261–1274, 2007. View at Publisher · View at Google Scholar · View at Scopus
  82. L. C. Cantley, “The phosphoinositide 3-kinase pathway,” Science, vol. 296, no. 5573, pp. 1655–1657, 2002. View at Publisher · View at Google Scholar · View at Scopus
  83. T. M. Morgan, T. D. Koreckij, and E. Corey, “Targeted therapy for advanced prostate cancer: inhibition of the PI3K/Akt/mTOR pathway,” Current Cancer Drug Targets, vol. 9, no. 2, pp. 237–249, 2009. View at Publisher · View at Google Scholar · View at Scopus
  84. A. Di Cristofano, B. Pesce, C. Cordon-Cardo, and P. P. Pandolfi, “Pten is essential for embryonic development and tumour suppression,” Nature Genetics, vol. 19, no. 4, pp. 348–355, 1998. View at Publisher · View at Google Scholar · View at Scopus
  85. J. L. Boormans, H. Korsten, A. C. J. Ziel-Van Der Made, G. J. L. H. Van Leenders, P. C. M. S. Verhagen, and J. Trapman, “E17K substitution in AKT1 in prostate cancer,” British Journal of Cancer, vol. 102, no. 10, pp. 1491–1494, 2010. View at Publisher · View at Google Scholar · View at Scopus
  86. L. C. Trotman, M. Niki, Z. A. Dotan et al., “Pten dose dictates cancer progression in the prostate,” PLoS Biology, vol. 1, no. 3, article E59, 2003. View at Publisher · View at Google Scholar · View at Scopus
  87. Z. Chen, L. C. Trotman, D. Shaffer et al., “Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis,” Nature, vol. 436, no. 7051, pp. 725–730, 2005. View at Publisher · View at Google Scholar · View at Scopus
  88. A. Di Cristofano, M. De Acetis, A. Koff, C. Cordon-Cardo, and P. P Pandolfi, “Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse,” Nature Genetics, vol. 27, no. 2, pp. 222–224, 2001. View at Publisher · View at Google Scholar · View at Scopus
  89. L. Poliseno, L. Salmena, L. Riccardi et al., “Identification of the miR-106b~25 microRNA cluster as a proto-oncogenic PTEN-targeting intron that cooperates with its host gene MCM7 in transformation,” Science Signaling, vol. 3, no. 117, article ra29, 2010. View at Publisher · View at Google Scholar · View at Scopus
  90. M. S. Song, L. Salmena, A. Carracedo et al., “The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network,” Nature, vol. 455, no. 7214, pp. 813–817, 2008. View at Publisher · View at Google Scholar · View at Scopus
  91. M. S. Song, L. Salmena, and P. P. Pandolfi, “The functions and regulation of the PTEN tumour suppressor,” Nature Reviews Molecular Cell Biology, vol. 13, pp. 283–296, 2012.
  92. A. Almasan and A. Ashkenazi, “Apo2L/TRAIL: apoptosis signaling, biology, and potential for cancer therapy,” Cytokine and Growth Factor Reviews, vol. 14, no. 3-4, pp. 337–348, 2003. View at Publisher · View at Google Scholar · View at Scopus
  93. J. Xu, J. Y. Zhou, W. Z. Wei, and G. S. Wu, “Activation of the Akt survival pathway contributes to TRAIL resistance in cancer cells,” PLoS ONE, vol. 5, no. 4, Article ID e10226, 2010. View at Publisher · View at Google Scholar · View at Scopus
  94. N. Tzenaki, M. Andreou, K. Stratigi et al., “High levels of p110delta PI3K expression in solid tumor cells suppress PTEN activity, generating cellular sensitivity to p110delta inhibitors through PTEN activation,” FASEB Journal, vol. 26, pp. 2498–2508, 2012.
  95. S. H. Lee, G. Poulogiannis, S. Pyne et al., “A constitutively activated form of the p110β isoform of PI3-kinase induces prostatic intraepithelial neoplasia in mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 24, pp. 11002–11007, 2010. View at Publisher · View at Google Scholar · View at Scopus
  96. B. Cinar, P. K. Fang, M. Lutchman et al., “The pro-apoptotic kinase Mst1 and its caspase cleavage products are direct inhibitors of Akt1,” EMBO Journal, vol. 26, no. 21, pp. 4523–4534, 2007. View at Publisher · View at Google Scholar · View at Scopus
  97. B. Cinar, F. K. Collak, D. Lopez et al., “MST1 is a multifunctional caspase-independent inhibitor of androgenic signaling,” Cancer Research, vol. 71, no. 12, pp. 4303–4313, 2011. View at Publisher · View at Google Scholar · View at Scopus
  98. Z. Yuan, D. Kim, S. Shu et al., “Phosphoinositide 3-kinase/Akt inhibits MST1-mediated pro-apoptotic signaling through phosphorylation of threonine 120,” Journal of Biological Chemistry, vol. 285, no. 6, pp. 3815–3824, 2010. View at Publisher · View at Google Scholar · View at Scopus
  99. K. Mahajan, D. Coppola, S. Challa et al., “Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its activation,” PloS ONE, vol. 5, no. 3, article e9646, 2010. View at Scopus
  100. K. Nacerddine, J. B. Beaudry, V. Ginjala et al., “Akt-mediated phosphorylation of Bmi1 modulates its oncogenic potential, E3 ligase activity, and DNA damage repair activity in mouse prostate cancer,” Journal of Clinical Investigation, vol. 122, pp. 1920–1932, 2012.
  101. M. Gao, R. Patel, I. Ahmad et al., “SPRY2 loss enhances ErbB trafficking and PI3K/AKT signalling to drive human and mouse prostate carcinogenesis,” EMBO Molecular Medicine, vol. 4, pp. 776–790, 2012.
  102. V. M. Adhami, I. A. Siddiqui, S. Sarfaraz et al., “Effective prostate cancer chemopreventive intervention with green tea polyphenols in the TRAMP model depends on Thestage of the disease,” Clinical Cancer Research, vol. 15, no. 6, pp. 1947–1953, 2009. View at Publisher · View at Google Scholar · View at Scopus
  103. V. M. Adhami, I. A. Siddiqui, N. Ahmad, S. Gupta, and H. Mukhtar, “Oral consumption of green tea polyphenols inhibits insulin-like growth factor-I-induced signaling in an autochthonous mouse model of prostate cancer,” Cancer Research, vol. 64, no. 23, pp. 8715–8722, 2004. View at Publisher · View at Google Scholar · View at Scopus
  104. H. J. Kung and C. P. Evans, “Oncogenic activation of androgen receptor,” Urologic Oncology, vol. 27, no. 1, pp. 48–52, 2009. View at Publisher · View at Google Scholar · View at Scopus
  105. N. J. Clegg, S. S. Couto, J. Wongvipat et al., “MYC cooperates with AKT in prostate tumorigenesis and alters sensitivity to mTOR inhibitors,” PLoS ONE, vol. 6, no. 3, Article ID e17449, 2011. View at Publisher · View at Google Scholar · View at Scopus
  106. D. N. Gunadharini, P. Elumalai, R. Arunkumar, K. Senthilkumar, and J. Arunakaran, “Induction of apoptosis and inhibition of PI3K/Akt pathway in PC-3 and LNCaP prostate cancer cells by ethanolic neem leaf extract,” Journal of Ethnopharmacology, vol. 134, no. 3, pp. 644–650, 2011. View at Publisher · View at Google Scholar · View at Scopus
  107. K. R. Park, D. Nam, H. M. Yun et al., “beta-Caryophyllene oxide inhibits growth and induces apoptosis through the suppression of PI3K/AKT/mTOR/S6K1 pathways and ROS-mediated MAPKs activation,” Cancer Letters, vol. 312, pp. 178–188, 2011.
  108. V. M. Adhami, D. N. Syed, N. Khan, and H. Mukhtar, “Dietary flavonoid fisetin: a novel dual inhibitor of PI3K/Akt and mTOR for prostate cancer management,” Biochemical Pharmacology, vol. 84, pp. 1277–1281, 2012.
  109. Z. Wang, Y. Zhang, S. Banerjee, Y. Li, and F. H. Sarkar, “Notch-1 down-regulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells,” Cancer, vol. 106, no. 11, pp. 2503–2513, 2006. View at Publisher · View at Google Scholar · View at Scopus
  110. M. J. Ryu, M. Cho, J. Y. Song et al., “Natural derivatives of curcumin attenuate the Wnt/β-catenin pathway through down-regulation of the transcriptional coactivator p300,” Biochemical and Biophysical Research Communications, vol. 377, no. 4, pp. 1304–1308, 2008. View at Publisher · View at Google Scholar · View at Scopus
  111. S. Yu, G. Shen, O. K. Tin, J. H. Kim, and A. N. T. Kong, “Curcumin inhibits Akt/mammalian target of rapamycin signaling through protein phosphatase-dependent mechanism,” Molecular Cancer Therapeutics, vol. 7, no. 9, pp. 2609–2620, 2008. View at Publisher · View at Google Scholar · View at Scopus
  112. A. Ślusarz, N. S. Shenouda, M. S. Sakla et al., “Common botanical compounds inhibit the hedgehog signaling pathway in prostate cancer,” Cancer Research, vol. 70, no. 8, pp. 3382–3390, 2010. View at Publisher · View at Google Scholar · View at Scopus
  113. O. W. Rokhlin, N. V. Guseva, A. F. Taghiyev, R. A. Glover, and M. B. Cohen, “KN-93 inhibits androgen receptor activity and induces cell death irrespective of p53 and Akt status in prostate cancer,” Cancer Biology and Therapy, vol. 9, no. 3, pp. 224–235, 2010. View at Publisher · View at Google Scholar · View at Scopus
  114. J. J. Wallin, K. A. Edgar, J. Guan et al., “GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway,” Molecular Cancer Therapeutics, vol. 10, pp. 2426–2436, 2011.
  115. S. M. Manohar, A. A. Padgaonkar, A. J. Badhwar et al., “A novel inhibitor of hypoxia-inducible factor-1alpha P3155 also modulates PI3K pathway and inhibits growth of prostate cancer cells,” BMC Cancer, vol. 11, article 338, 2011. View at Publisher · View at Google Scholar · View at Scopus
  116. L. Lu, D. Tang, L. Wang et al., “Gambogic acid inhibits TNF-alpha-induced invasion of human prostate cancer PC3 cells in vitro through PI3K/Akt and NF-kappaB signaling pathways,” Acta Pharmacologica Sinica, vol. 33, pp. 531–541, 2012.
  117. S. L. Burgio, F. Fabbri, I. J. Seymour, W. Zoli, D. Amadori, and U. De Giorgi, “Perspectives on mTOR inhibitors for castration-refractory prostate cancer,” Current Cancer Drug Targets, vol. 12, pp. 940–949, 2012.
  118. E. C. Nelson, C. P. Evans, P. C. Mack, R. W. Devere-White, and P. N. Lara Jr., “Inhibition of Akt pathways in the treatment of prostate cancer,” Prostate Cancer and Prostatic Diseases, vol. 10, no. 4, pp. 331–339, 2007. View at Publisher · View at Google Scholar · View at Scopus
  119. C. A. Granville, R. M. Memmott, J. J. Gills, and P. A. Dennis, “Handicapping the race to develop inhibitors of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin pathway,” Clinical Cancer Research, vol. 12, no. 3, pp. 679–689, 2006. View at Publisher · View at Google Scholar · View at Scopus
  120. S. B. Kondapaka, S. S. Singh, G. P. Dasmahapatra, E. A. Sausville, and K. K. Roy, “Perifosine, a novel alkylphospholipid, inhibits protein kinase B activation,” Molecular Cancer Therapeutics, vol. 2, no. 11, pp. 1093–1103, 2003. View at Scopus
  121. C. G. Tepper, R. L. Vinall, C. B. Wee et al., “GCP-mediated growth inhibition and apoptosis of prostate cancer cells via androgen receptor-dependent and -independent mechanisms,” Prostate, vol. 67, no. 5, pp. 521–535, 2007. View at Publisher · View at Google Scholar · View at Scopus
  122. P. B. Makhov, K. Golovine, A. Kutikov et al., “Modulation of Akt/mTOR signaling overcomes sunitinib resistance in renal and prostate cancer cells,” Molecular Cancer Therapeutics, vol. 11, pp. 1510–1517, 2012.
  123. H. Kiu and S. E. Nicholson, “Biology and significance of the JAK/STAT signalling pathways,” Growth Factors, vol. 30, pp. 88–106, 2012.
  124. D. A. Harrison, “The Jak/STAT pathway,” Cold Spring Harbor Perspectives in Biology, vol. 4, 2012.
  125. W. X. Li, “Canonical and non-canonical JAK-STAT signaling,” Trends in Cell Biology, vol. 18, no. 11, pp. 545–551, 2008. View at Publisher · View at Google Scholar · View at Scopus
  126. D. Hebenstreit, J. Horejs-Hoeck, and A. Duschl, “JAK/STAT-dependent gene regulation by cytokines,” Drug News and Perspectives, vol. 18, no. 4, pp. 243–249, 2005. View at Publisher · View at Google Scholar · View at Scopus
  127. J. J. O'Shea, H. Park, M. Pesu, D. Borie, and P. Changelian, “New strategies for immunosuppression: interfering with cytokines by targeting the Jak/Stat pathway,” Current Opinion in Rheumatology, vol. 17, no. 3, pp. 305–311, 2005. View at Publisher · View at Google Scholar · View at Scopus
  128. P. Igaz, S. Tóth, and A. Falus, “Biological and clinical significance of the JAK-STAT pathway; lessons from knockout mice,” Inflammation Research, vol. 50, no. 9, pp. 435–441, 2001. View at Scopus
  129. J. J. O'Shea, M. Gadina, and R. D. Schreiber, “Cytokine signaling in 2002: new surprises in the Jak/Stat pathway,” Cell, vol. 109, no. 2, pp. S121–S131, 2002. View at Publisher · View at Google Scholar · View at Scopus
  130. J. E. Darnell Jr., “STATs and gene regulation,” Science, vol. 277, no. 5332, pp. 1630–1635, 1997. View at Publisher · View at Google Scholar · View at Scopus
  131. J. N. Ihle, W. Thierfelder, S. Teglund et al., “Signaling by the cytokine receptor superfamily,” Annals of the New York Academy of Sciences, vol. 865, pp. 1–9, 1998. View at Publisher · View at Google Scholar · View at Scopus
  132. K. Shuai, C. M. Horvath, L. H. T. Huang, S. A. Qureshi, D. Cowburn, and J. E. Darnell Jr., “Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions,” Cell, vol. 76, no. 5, pp. 821–828, 1994. View at Publisher · View at Google Scholar · View at Scopus
  133. S. Gupta, T. Barrett, A. J. Whitmarsh et al., “Selective interaction of JNK protein kinase isoforms with transcription factors,” EMBO Journal, vol. 15, no. 11, pp. 2760–2770, 1996. View at Scopus
  134. K. Mowen and M. David, “Role of the STAT1-SH2 domain and STAT2 in the activation and nuclear translocation of STAT1,” Journal of Biological Chemistry, vol. 273, no. 46, pp. 30073–30076, 1998. View at Publisher · View at Google Scholar · View at Scopus
  135. J. S. Rawlings, K. M. Rosler, and D. A. Harrison, “The JAK/STAT signaling pathway,” Journal of Cell Science, vol. 117, no. 8, pp. 1281–1283, 2004. View at Publisher · View at Google Scholar · View at Scopus
  136. J. Bromberg, “Stat proteins and oncogenesis,” Journal of Clinical Investigation, vol. 109, no. 9, pp. 1139–1142, 2002. View at Publisher · View at Google Scholar · View at Scopus
  137. H. Yu and R. Jove, “The stats of cancer—new molecular targets come of age,” Nature Reviews Cancer, vol. 4, no. 2, pp. 97–105, 2004. View at Scopus
  138. A. Tutt and A. Ashworth, “The relationship between the roles of BRCA genes in DNA repair and cancer predisposition,” Trends in Molecular Medicine, vol. 8, no. 12, pp. 571–576, 2002. View at Publisher · View at Google Scholar · View at Scopus
  139. H. Wallerand, G. Robert, J. C. Bernhard, A. Ravaud, and J. J. Patard, “Tyrosine-kinase inhibitors in the treatment of muscle invasive bladder cancer and hormone refractory prostate cancer,” Archivos Espanoles de Urologia, vol. 63, no. 9, pp. 773–787, 2010. View at Scopus
  140. E. M. Kwon, S. K. Holt, R. Fu et al., “Androgen metabolism and JAK/STAT pathway genes and prostate cancer risk,” Cancer Epidemiology, vol. 36, pp. 347–353, 2012.
  141. D. A. Frank, “STAT3 as a central mediator of neoplastic cellular transformation,” Cancer Letters, vol. 251, no. 2, pp. 199–210, 2007. View at Publisher · View at Google Scholar · View at Scopus
  142. B. Gao, X. Shen, G. Kunos et al., “Constitutive activation of JAK-STAT3 signaling by BRCA1 in human prostate cancer cells,” FEBS Letters, vol. 488, no. 3, pp. 179–184, 2001. View at Publisher · View at Google Scholar · View at Scopus
  143. A. R. Venkitaraman, “Cancer susceptibility and the functions of BRCA1 and BRCA2,” Cell, vol. 108, no. 2, pp. 171–182, 2002. View at Publisher · View at Google Scholar · View at Scopus
  144. E. A. Ostrander and M. S. Udler, “The role of the BRCA2 gene in susceptibility to prostate cancer revisited,” Cancer Epidemiology Biomarkers and Prevention, vol. 17, no. 8, pp. 1843–1848, 2008. View at Publisher · View at Google Scholar · View at Scopus
  145. S. Panchal, O. Shachar, F. O'Malley et al., “Breast cancer in a BRCA2 mutation carrier with a history of prostate cancer,” Nature Reviews Clinical Oncology, vol. 6, no. 10, pp. 604–607, 2009. View at Publisher · View at Google Scholar · View at Scopus
  146. N. Rahman and M. R. Stratton, “The genetics of breast cancer susceptibility,” Annual Review of Genetics, vol. 32, pp. 95–121, 1998. View at Publisher · View at Google Scholar · View at Scopus
  147. P. Kerr and A. Ashworth, “New complexities for BRCA1 and BRCA2,” Current Biology, vol. 11, no. 16, pp. R668–R676, 2001. View at Publisher · View at Google Scholar · View at Scopus
  148. M. Sakaguchi, M. Oka, T. Iwasaki, Y. Fukami, and C. Nishigori, “Role and regulation of STAT3 phosphorylation at Ser727 in melanocytes and melanoma cells,” Journal of Investigative Dermatology, vol. 132, pp. 1877–1885, 2012.
  149. J. Cao, P. Kozarekar, M. Pavlaki, C. Chiarelli, W. F. Bahou, and S. Zucker, “Distinct roles for the catalytic and hemopexin domains of membrane type 1-matrix metalloproteinase in substrate degradation and cell migration,” Journal of Biological Chemistry, vol. 279, no. 14, pp. 14129–14139, 2004. View at Publisher · View at Google Scholar · View at Scopus
  150. V. I. Romanov, T. Whyard, H. L. Adler, W. C. Waltzer, and S. Zucker, “Prostate cancer cell adhesion to bone marrow endothelium: the role of prostate-specific antigen,” Cancer Research, vol. 64, no. 6, pp. 2083–2089, 2004. View at Publisher · View at Google Scholar · View at Scopus
  151. H. L. Nguyen, S. Zucker, K. Zarrabi, P. Kadam, C. Schmidt, and J. Cao, “Oxidative stress and prostate cancer progression are elicited by membrane-type 1 matrix metalloproteinase,” Molecular Cancer Research, vol. 9, pp. 1305–1318, 2011.
  152. D. Kesanakurti, C. Chetty, D. H. Dinh, M. Gujrati, and J. S. Rao, “Role of MMP-2 in the regulation of IL-6/Stat3 survival signaling via interaction with alpha5beta1 integrin in glioma,” Oncogene, vol. 32, pp. 327–340, 2012.
  153. R. Dhir, Z. Ni, W. Lou, F. DeMiguel, J. R. Grandis, and A. C. Gao, “Stat3 activation in prostatic carcinomas,” Prostate, vol. 51, no. 4, pp. 241–246, 2002. View at Publisher · View at Google Scholar · View at Scopus
  154. X. Liu, Z. He, C. H. Li, G. Huang, C. Ding, and H. Liu, “Correlation analysis of JAK-STAT pathway components on prognosis of patients with prostate cancer,” Pathology and Oncology Research, vol. 18, pp. 17–23, 2012.
  155. R. Aalinkeel, Z. Hu, B. B. Nair et al., “Genomic analysis highlights the role of the JAK-STAT signaling in the anti-proliferative effects of dietary—flavonoid “ashwagandha” in prostate cancer cells,” Evidence-Based Complementary and Alternative Medicine, vol. 7, no. 2, pp. 177–187, 2010. View at Publisher · View at Google Scholar · View at Scopus
  156. K. Ishihara and T. Hirano, “IL-6 in autoimmune disease and chronic inflammatory proliferative disease,” Cytokine and Growth Factor Reviews, vol. 13, no. 4-5, pp. 357–368, 2002. View at Publisher · View at Google Scholar · View at Scopus
  157. T. Kishimoto, “Interleukin-6: from basic science to medicine—40 years in immunology,” Annual Review of Immunology, vol. 23, pp. 1–21, 2005. View at Publisher · View at Google Scholar · View at Scopus
  158. A. Hobisch, H. Rogatsch, A. Hittmair, et al., “Immunohistochemical localization of interleukin-6 and its receptor in benign, premalignant and malignant prostate tissue,” Journal of Pathology, vol. 191, pp. 239–244, 2000.
  159. P. C. Smith, A. Hobisch, D. L. Lin, Z. Culig, and E. T. Keller, “Interleukin-6 and prostate cancer progression,” Cytokine and Growth Factor Reviews, vol. 12, no. 1, pp. 33–40, 2001. View at Publisher · View at Google Scholar · View at Scopus
  160. J. R. Stark, H. Li, P. Kraft et al., “Circulating prediagnostic interleukin-6 and C-reactive protein and prostate cancer incidence and mortality,” International Journal of Cancer, vol. 124, no. 11, pp. 2683–2689, 2009. View at Publisher · View at Google Scholar · View at Scopus
  161. J. Karkera, H. Steiner, W. Li et al., “The anti-interleukin-6 antibody siltuximab down-regulates genes implicated in tumorigenesis in prostate cancer patients from a phase I study,” Prostate, vol. 71, pp. 1455–1465, 2011.
  162. D. A. Twillie, M. A. Eisenberger, M. A. Carducci, W. S. Hseih, W. Y. Kim, and J. W. Simons, “Interleukin-6: a candidate mediator of human prostate cancer morbidity,” Urology, vol. 45, no. 3, pp. 542–549, 1995. View at Publisher · View at Google Scholar · View at Scopus
  163. M. Okamoto, C. Lee, and R. Oyasu, “Interleukin-6 as a paracrine and autocrine growth factor in human prostatic carcinoma cells in vitro,” Cancer Research, vol. 57, no. 1, pp. 141–146, 1997. View at Scopus
  164. I. T. Cavarretta, H. Neuwirt, G. Untergasser et al., “The antiapoptotic effect of IL-6 autocrine loop in a cellular model of advanced prostate cancer is mediated by Mcl-1,” Oncogene, vol. 26, no. 20, pp. 2822–2832, 2007. View at Publisher · View at Google Scholar · View at Scopus
  165. T. D. Chung, J. J. Yu, M. T. Spiotto, M. Bartkowski, and J. W. Simons, “Characterization of the role of IL-6 in the progression of prostate cancer,” Prostate, vol. 38, pp. 199–207, 1999.
  166. W. Lou, Z. Ni, K. Dyer, D. J. Tweardy, and A. C. Gao, “Interleukin-6 induces prostate cancer cell growth accompanied by activation of stat3 signaling pathway,” Prostate, vol. 42, pp. 239–242, 2000.
  167. I. Sakai, H. Miyake, T. Terakawa, and M. Fujisawa, “Inhibition of tumor growth and sensitization to chemotherapy by RNA interference targeting interleukin-6 in the androgen-independent human prostate cancer PC3 model,” Cancer Science, vol. 102, no. 4, pp. 769–775, 2011. View at Publisher · View at Google Scholar · View at Scopus
  168. L. R. Dearth and J. DeWille, “An AU-rich element in the 3 untranslated region of the C/EBPδ mRNA is important for protein binding during G0 growth arrest,” Biochemical and Biophysical Research Communications, vol. 304, no. 2, pp. 344–350, 2003. View at Publisher · View at Google Scholar · View at Scopus
  169. L. R. Dearth and J. DeWille, “Posttranscriptional and posttranslational regulation of C/EBPδ in Go growth-arrested mammary epithelial cells,” Journal of Biological Chemistry, vol. 278, no. 13, pp. 11246–11255, 2003. View at Publisher · View at Google Scholar · View at Scopus
  170. D. P. Ramji and P. Foka, “CCAAT/enhancer-binding proteins: structure, function and regulation,” Biochemical Journal, vol. 365, no. 3, pp. 561–575, 2002. View at Publisher · View at Google Scholar · View at Scopus
  171. D. C. Sanford and J. W. DeWille, “C/EBPδ is a downstream mediator of IL-6 induced growth inhibition of prostate cancer cells,” Prostate, vol. 63, no. 2, pp. 143–154, 2005. View at Publisher · View at Google Scholar · View at Scopus
  172. E. LaTulippe, J. Satagopan, A. Smith et al., “Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease,” Cancer Research, vol. 62, no. 15, pp. 4499–4506, 2002. View at Scopus
  173. B. Binétruy, L. Heasley, F. Bost, L. Caron, and M. Aouadi, “Concise review: regulation of embryonic stem cell lineage commitment by mitogen-activated protein kinases,” Stem Cells, vol. 25, no. 5, pp. 1090–1095, 2007. View at Publisher · View at Google Scholar · View at Scopus
  174. A. S. Dhillon, S. Hagan, O. Rath, and W. Kolch, “MAP kinase signalling pathways in cancer,” Oncogene, vol. 26, no. 22, pp. 3279–3290, 2007. View at Publisher · View at Google Scholar · View at Scopus
  175. E. F. Wagner and A. R. Nebreda, “Signal integration by JNK and p38 MAPK pathways in cancer development,” Nature Reviews Cancer, vol. 9, no. 8, pp. 537–549, 2009. View at Publisher · View at Google Scholar · View at Scopus
  176. Y. T. Ip and R. J. Davis, “Signal transduction by the c-Jun N-terminal kinase (JNK)—from inflammation to development,” Current Opinion in Cell Biology, vol. 10, no. 2, pp. 205–219, 1998. View at Publisher · View at Google Scholar · View at Scopus
  177. T. H. Holmström, I. Schmitz, T. S. Söderström et al., “MAPK/ERK signaling in activated T cells inhibits CD95/Fas-mediated apoptosis downstream of DISC assembly,” EMBO Journal, vol. 19, no. 20, pp. 5418–5428, 2000. View at Scopus
  178. K. Gupta, S. Kshirsagar, W. Li et al., “VEGF prevents apoptosis of human microvascular endothelial cells via opposing effects on MAPK/ERK and SAPK/JNK signaling,” Experimental Cell Research, vol. 247, no. 2, pp. 495–504, 1999. View at Publisher · View at Google Scholar · View at Scopus
  179. A. Ogata, D. Chauhan, G. Teoh et al., “IL-6 triggers cell growth via the ras-dependent mitogen-activated protein kinase cascade,” Journal of Immunology, vol. 159, no. 5, pp. 2212–2221, 1997. View at Scopus
  180. V. Flati, E. Pasini, G. D'Antona, S. Speca, E. Toniato, and S. Martinotti, “Intracellular mechanisms of metabolism regulation: the role of signaling via the mammalian target of rapamycin pathway and other routes,” American Journal of Cardiology, vol. 101, no. 11, pp. S16–S21, 2008. View at Publisher · View at Google Scholar · View at Scopus
  181. S. Davis, P. Vanhoutte, C. Pagès, J. Caboche, and S. Laroche, “The MAPK/ERK cascade targets both Elk-1 and cAMP response element- binding protein to control long-term potentiation-dependent gene expression in the dentate gyrus in vivo,” Journal of Neuroscience, vol. 20, no. 12, pp. 4563–4572, 2000. View at Scopus
  182. J. Guicheux, J. Lemonnier, C. Ghayor, A. Suzuki, G. Palmer, and J. Caverzasio, “Activation of p38 mitogen-activated protein kinase and c-Jun-NH2-terminal kinase by BMP-2 and their implication in the stimulation of osteoblastic cell differentiation,” Journal of Bone and Mineral Research, vol. 18, no. 11, pp. 2060–2068, 2003. View at Publisher · View at Google Scholar · View at Scopus
  183. C. Huang, K. Jacobson, and M. D. Schaller, “MAP kinases and cell migration,” Journal of Cell Science, vol. 117, no. 20, pp. 4619–4628, 2004. View at Publisher · View at Google Scholar · View at Scopus
  184. M. A. Lemmon and J. Schlessinger, “Cell signaling by receptor tyrosine kinases,” Cell, vol. 141, no. 7, pp. 1117–1134, 2010. View at Publisher · View at Google Scholar · View at Scopus
  185. L. A. Fecher, R. K. Amaravadi, and K. T. Flaherty, “The MAPK pathway in melanoma,” Current Opinion in Oncology, vol. 20, no. 2, pp. 183–189, 2008. View at Publisher · View at Google Scholar · View at Scopus
  186. Y. Fleming, C. G. Armstrong, N. Morrice, A. Paterson, M. Goedert, and P. Cohen, “Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein kinase kinase 4 (MKK4) and MKK7,” Biochemical Journal, vol. 352, no. 1, pp. 145–154, 2000. View at Publisher · View at Google Scholar · View at Scopus
  187. W. Haeusgen, T. Herdegen, and V. Waetzig, “The bottleneck of JNK signaling: molecular and functional characteristics of MKK4 and MKK7,” European Journal of Cell Biology, vol. 90, no. 6-7, pp. 536–544, 2011. View at Publisher · View at Google Scholar · View at Scopus
  188. W. Xin, K. J. Yun, F. Ricci et al., “MAP2K4/MKK4 expression in pancreatic cancer: genetic validation of immunohistochemistry and relationship to disease course,” Clinical Cancer Research, vol. 10, no. 24, pp. 8516–8520, 2004. View at Publisher · View at Google Scholar · View at Scopus
  189. S. D. Yamada, J. A. Hickson, Y. Hrobowski et al., “Mitogen-activated protein kinase kinase 4 (MKK4) acts as a metastasis suppressor gene in human ovarian carcinoma,” Cancer Research, vol. 62, no. 22, pp. 6717–6723, 2002. View at Scopus
  190. R. Chiu, W. J. Boyle, J. Meek, T. Smeal, T. Hunter, and M. Karin, “The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes,” Cell, vol. 54, no. 4, pp. 541–552, 1988. View at Scopus
  191. C. Jonat, H. J. Rahmsdorf, K. K. Park et al., “Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone,” Cell, vol. 62, no. 6, pp. 1189–1204, 1990. View at Publisher · View at Google Scholar · View at Scopus
  192. C. W. Kinkade, M. Castillo-Martin, A. Puzio-Kuter et al., “Targeting AKT/mTOR and ERK MAPK signaling inhibits hormone-refractory prostate cancer in a preclinical mouse model,” Journal of Clinical Investigation, vol. 118, no. 9, pp. 3051–3064, 2008. View at Publisher · View at Google Scholar · View at Scopus
  193. M. T. Abreu-Martin, A. Chari, A. A. Palladino, N. A. Craft, and C. L. Sawyers, “Mitogen-activated protein kinase kinase kinase 1 activates androgen receptor-dependent transcription and apoptosis in prostate cancer,” Molecular and Cellular Biology, vol. 19, no. 7, pp. 5143–5154, 1999. View at Scopus
  194. D. Gioeli, J. W. Mandell, G. R. Petroni, H. F. Frierson, and M. J. Weber, “Activation of mitogen-activated protein kinase associated with prostate cancer progression,” Cancer Research, vol. 59, no. 2, pp. 279–284, 1999. View at Scopus
  195. A. M. Carey, R. Pramanik, L. J. Nicholson et al., “Ras-MEK-ERK signaling cascade regulates androgen receptor element-inducible gene transcription and DNA synthesis in prostate cancer cells,” International Journal of Cancer, vol. 121, no. 3, pp. 520–527, 2007. View at Publisher · View at Google Scholar · View at Scopus
  196. T. J. Dorkin, M. C. Robinson, C. Marsh, A. Bjartell, D. E. Neal, and H. Y. Leung, “FGF8 over-expression in prostate cancer is associated with decreased patient survival and persists in androgen independent disease,” Oncogene, vol. 18, no. 17, pp. 2755–2761, 1999. View at Publisher · View at Google Scholar · View at Scopus
  197. H. Steiner, S. Godoy-Tundidor, H. Rogatsch et al., “Accelerated in vivo growth of prostate tumors that up-regulate interleukin-6 is associated with reduced retinoblastoma protein expression and activation of the mitogen-activated protein kinase pathway,” American Journal of Pathology, vol. 162, no. 2, pp. 655–663, 2003. View at Scopus
  198. R. E. Bakin, D. Gioeli, E. A. Bissonette, and M. J. Weber, “Attenuation of Ras signaling restores androgen sensitivity to hormone-refractory C4-2 prostate cancer cells,” Cancer Research, vol. 63, no. 8, pp. 1975–1980, 2003. View at Scopus
  199. J. H. Jeong, Z. Wang, A. S. Guimaraes et al., “BRAF activation initiates but does not maintain invasive prostate adenocarcinoma,” PLoS ONE, vol. 3, no. 12, Article ID e3949, 2008. View at Publisher · View at Google Scholar · View at Scopus
  200. H. B. Pearson, T. J. Phesse, and A. R. Clarke, “K-ras and Wnt signaling synergize to accelerate prostate tumorigenesis in the mouse,” Cancer Research, vol. 69, no. 1, pp. 94–101, 2009. View at Publisher · View at Google Scholar · View at Scopus
  201. N. Palanisamy, B. Ateeq, S. Kalyana-Sundaram et al., “Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma,” Nature Medicine, vol. 16, no. 7, pp. 793–798, 2010. View at Publisher · View at Google Scholar · View at Scopus
  202. L. Tie, N. Lu, X. Y. Pan et al., “Hypoxia-induced up-regulation of aquaporin-1 protein in prostate cancer cells in a p38-dependent manner,” Cellular Physiology and Biochemistry, vol. 29, pp. 269–280, 2012.
  203. Y. Limami, A. Pinon, D. Y. Leger et al., “The P2Y2/Src/p38/COX-2 pathway is involved in the resistance to ursolic acid-induced apoptosis in colorectal and prostate cancer cells,” Biochimie, vol. 94, pp. 1754–1763, 2012.
  204. M. Katoh, “FGFR2 abnormalities underlie a spectrum of bone, skin, and cancer pathologies,” Journal of Investigative Dermatology, vol. 129, no. 8, pp. 1861–1867, 2009. View at Publisher · View at Google Scholar · View at Scopus
  205. P. C. Marker, A. A. Donjacour, R. Dahiya, and G. R. Cunha, “Hormonal, cellular, and molecular control of prostatic development,” Developmental Biology, vol. 253, no. 2, pp. 165–174, 2003. View at Publisher · View at Google Scholar · View at Scopus
  206. A. A. Donjacour, A. A. Thomson, and G. R. Cunha, “FGF-10 plays an essential role in the growth of the fetal prostate,” Developmental Biology, vol. 261, no. 1, pp. 39–54, 2003. View at Publisher · View at Google Scholar · View at Scopus
  207. Y. Lin, G. Liu, Y. Zhang et al., “Fibroblast growth factor receptor 2 tyrosine kinase is required for prostatic morphogenesis and the acquisition of strict androgen dependency for adult tissue homeostasis,” Development, vol. 134, no. 4, pp. 723–734, 2007. View at Publisher · View at Google Scholar · View at Scopus
  208. Y. Zhang, J. Zhang, Y. Lin et al., “Role of epithelial cell fibroblast growth factor receptor substrate 2α in prostate development, regeneration and tumorigenesis,” Development, vol. 135, no. 4, pp. 775–784, 2008. View at Publisher · View at Google Scholar · View at Scopus
  209. S. L. Kuslak and P. C. Marker, “Fibroblast growth factor receptor signaling through MEK-ERK is required for prostate bud induction,” Differentiation, vol. 75, no. 7, pp. 638–651, 2007. View at Publisher · View at Google Scholar · View at Scopus
  210. M. J. Hour, S. C. Tsai, H. C. Wu et al., “Antitumor effects of the novel quinazolinone MJ-33: inhibition of metastasis through the MAPK, AKT, NF-kappaB and AP-1 signaling pathways in DU145 human prostate cancer cells,” International Journal of Oncology, 2012.
  211. T. Shimizu, A. W. Tolcher, K. P. Papadopoulos et al., “The clinical effect of the dual-targeting strategy involving PI3K/AKT/mTOR and RAS/MEK/ERK pathways in patients with advanced cancer,” Clinical Cancer Research, vol. 18, pp. 2316–2325, 2012.
  212. G. C. Blobe, W. P. Schiemann, and H. F. Lodish, “Role of transforming growth factor β in human disease,” New England Journal of Medicine, vol. 342, no. 18, pp. 1350–1358, 2000. View at Publisher · View at Google Scholar · View at Scopus
  213. J. Massagué, S. W. Blain, and R. S. Lo, “TGFβ signaling in growth control, cancer, and heritable disorders,” Cell, vol. 103, no. 2, pp. 295–309, 2000. View at Scopus
  214. B. Schmierer and C. S. Hill, “TGFβ-SMAD signal transduction: molecular specificity and functional flexibility,” Nature Reviews Molecular Cell Biology, vol. 8, no. 12, pp. 970–982, 2007. View at Publisher · View at Google Scholar · View at Scopus
  215. J. Massague, “TGFbeta in cancer,” Cell, vol. 134, pp. 215–230, 2008.
  216. Y. Shi and J. Massagué, “Mechanisms of TGF-β signaling from cell membrane to the nucleus,” Cell, vol. 113, no. 6, pp. 685–700, 2003. View at Publisher · View at Google Scholar · View at Scopus
  217. F. L. Miles, N. S. Tung, A. A. Aguiar, S. Kurtoglu, and R. A. Sikes, “Increased TGF-beta1-mediated suppression of growth and motility in castrate-resistant prostate cancer cells is consistent with Smad2/3 signaling,” Prostate, vol. 72, pp. 1339–1350, 2012.
  218. M. K. Donkor, A. Sarkar, and M. O. Li, “Tgf-beta1 produced by activated CD4+ T cells antagonizes T cell surveillance of tumor development,” Oncoimmunology, vol. 1, pp. 162–171, 2012.
  219. X. Wan, Z. G. Li, J. M. Yingling et al., “Effect of transforming growth factor beta (TGF-beta) receptor I kinase inhibitor on prostate cancer bone growth,” Bone, vol. 50, pp. 695–703, 2012.
  220. P. Wikstrom, P. Stattin, I. Franck-Lissbrant, J. E. Damber, and A. Bergh, “Transforming growth factor beta1 is associated with angiogenesis, metastasis, and poor clinical outcome in prostate cancer,” Prostate, vol. 37, pp. 19–29, 1998.
  221. H. L. Adler, M. A. McCurdy, M. W. Kattan, T. L. Timme, P. T. Scardino, and T. C. Thompson, “Elevated levels of circulating interleukin-6 and transforming growth factor-β1 in patients with metastatic prostatic carcinoma,” Journal of Urology, vol. 161, no. 1, pp. 182–187, 1999. View at Publisher · View at Google Scholar · View at Scopus
  222. S. F. Shariat, M. Shalev, A. Menesses-Diaz et al., “Preoperative plasma levels of transforming growth factor beta1 (TGF-β1 strongly predict progression in patients undergoing radical prostatectomy,” Journal of Clinical Oncology, vol. 19, no. 11, pp. 2856–2864, 2001. View at Scopus
  223. R. Derynck, R. J. Akhurst, and A. Balmain, “TGF-β signaling in tumor suppression and cancer progression,” Nature Genetics, vol. 29, no. 2, pp. 117–129, 2001. View at Publisher · View at Google Scholar · View at Scopus
  224. L. M. Wakefield and A. B. Roberts, “TGF-β signaling: positive and negative effects on tumorigenesis,” Current Opinion in Genetics and Development, vol. 12, no. 1, pp. 22–29, 2002. View at Publisher · View at Google Scholar · View at Scopus
  225. J. Yang, R. Wahdan-Alaswad, and D. Danielpour, “Critical role of smad2 in tumor suppression and transforming growth factor-β-Lnduced apoptosis of prostate epithelial cells,” Cancer Research, vol. 69, no. 6, pp. 2185–2190, 2009. View at Publisher · View at Google Scholar · View at Scopus
  226. L. Ye, H. Kynaston, and W. G. Jiang, “Bone morphogenetic protein-10 suppresses the growth and aggressiveness of prostate cancer cells through a Smad independent pathway,” Journal of Urology, vol. 181, no. 6, pp. 2749–2759, 2009. View at Publisher · View at Google Scholar · View at Scopus
  227. B. T. Vo and S. A. Khan, “Expression of nodal and nodal receptors in prostate stem cells and prostate cancer cells: autocrine effects on cell proliferation and migration,” Prostate, vol. 71, no. 10, pp. 1084–1096, 2011. View at Publisher · View at Google Scholar · View at Scopus
  228. H. Y. Kang, H. Y. Huang, C. Y. Hsieh et al., “Activin A enhances prostate cancer cell migration through activation of androgen receptor and is overexpressed in metastatic prostate cancer,” Journal of Bone and Mineral Research, vol. 24, no. 7, pp. 1180–1193, 2009. View at Publisher · View at Google Scholar · View at Scopus
  229. J. L. Whyte, A. A. Smith, and J. A. Helms, “Wnt signaling and injury repair,” Cold Spring Harbor Perspectives in Biology, vol. 4, Article ID a008078, 2012.
  230. S. Angers and R. T. Moon, “Proximal events in Wnt signal transduction,” Nature Reviews Molecular Cell Biology, vol. 10, no. 7, pp. 468–477, 2009. View at Publisher · View at Google Scholar · View at Scopus
  231. S. Thiele, M. Rauner, C. Goettsch et al., “Expression profile of WNT molecules in prostate cancer and its regulation by aminobisphosphonates,” Journal of Cellular Biochemistry, vol. 112, no. 6, pp. 1593–1600, 2011. View at Publisher · View at Google Scholar · View at Scopus
  232. W. Lu, H. N. Tinsley, A. Keeton, Z. Qu, G. A. Piazza, and Y. Li, “Suppression of Wnt/β-catenin signaling inhibits prostate cancer cell proliferation,” European Journal of Pharmacology, vol. 602, no. 1, pp. 8–14, 2009. View at Publisher · View at Google Scholar · View at Scopus
  233. C. L. Hall, S. Kang, O. A. MacDougald, and E. T. Keller, “Role of Wnts in prostate cancer bone metastases,” Journal of Cellular Biochemistry, vol. 97, no. 4, pp. 661–672, 2006. View at Publisher · View at Google Scholar · View at Scopus
  234. D. Kimelman and W. Xu, “β-Catenin destruction complex: insights and questions from a structural perspective,” Oncogene, vol. 25, no. 57, pp. 7482–7491, 2006. View at Publisher · View at Google Scholar · View at Scopus
  235. J. Huelsken and J. Behrens, “The Wnt signalling pathway,” Journal of Cell Science, vol. 115, no. 21, pp. 3977–3978, 2002. View at Publisher · View at Google Scholar · View at Scopus
  236. H. C. Whitaker, J. Girling, A. Y. Warren, H. Leung, I. G. Mills, and D. E. Neal, “Alterations in β-catenin expression and localization in prostate cancer,” Prostate, vol. 68, no. 11, pp. 1196–1205, 2008. View at Publisher · View at Google Scholar · View at Scopus
  237. S. Majid, S. Saini, and R. Dahiya, “Wnt signaling pathways in urological cancers: past decades and still growing,” Molecular Cancer, vol. 11, article 7, 2012.
  238. S. Barolo, “Transgenic Wnt/TCF pathway reporters: all you need is Lef?” Oncogene, vol. 25, no. 57, pp. 7505–7511, 2006. View at Publisher · View at Google Scholar · View at Scopus
  239. C. Mosimann, G. Hausmann, and K. Basler, “β-Catenin hits chromatin: regulation of Wnt target gene activation,” Nature Reviews Molecular Cell Biology, vol. 10, no. 4, pp. 276–286, 2009. View at Publisher · View at Google Scholar · View at Scopus
  240. J. Zhao, W. Yue, M. J. Zhu, N. Sreejayan, and M. Du, “AMP-activated protein kinase (AMPK) cross-talks with canonical Wnt signaling via phosphorylation of beta-catenin at Ser 552,” Biochemical and Biophysical Research Communications, vol. 395, no. 1, pp. 146–151, 2010. View at Publisher · View at Google Scholar · View at Scopus
  241. W. J. Gullick, “Prevalence of aberrant expression of the epidermal growth factor receptor in human cancers,” British Medical Bulletin, vol. 47, no. 1, pp. 87–98, 1991. View at Scopus
  242. K. K. Guturi, T. Mandal, A. Chatterjee et al., “Mechanism of beta-catenin-mediated transcriptional regulation of epidermal growth factor receptor expression in glycogen synthase kinase 3 beta-inactivated prostate cancer cells,” Journal of Biological Chemistry, vol. 287, pp. 18287–18296, 2012.
  243. P. C. Marker, “Does prostate cancer co-opt the developmental program?” Differentiation, vol. 76, no. 6, pp. 736–744, 2008. View at Publisher · View at Google Scholar · View at Scopus
  244. N. S. Fearnhead, M. P. Britton, and W. F. Bodmer, “The ABC of APC,” Human Molecular Genetics, vol. 10, no. 7, pp. 721–733, 2001. View at Scopus
  245. D. R. Chesire, C. M. Ewing, J. Sauvageot, G. S. Bova, and W. B. Isaacs, “Detection and analysis of beta-catenin mutations in prostate cancer,” Prostate, vol. 45, pp. 323–334, 2000.
  246. L. Richiardi, V. Fiano, L. Vizzini et al., “Promoter methylation in APC, RUNX3, and GSTP1 and mortality in prostate cancer patients,” Journal of Clinical Oncology, vol. 27, no. 19, pp. 3161–3168, 2009. View at Publisher · View at Google Scholar · View at Scopus
  247. L. E. Pascal, R. Z. N. Vêncio, L. S. Page et al., “Gene expression relationship between prostate cancer cells of Gleason 3, 4 and normal epithelial cells as revealed by cell type-specific transcriptomes,” BMC Cancer, vol. 9, article 452, 2009. View at Publisher · View at Google Scholar · View at Scopus
  248. C. M. Koh, C. J. Bieberich, C. V. Dang, W. G. Nelson, S. Yegnasubramanian, and A. M. De Marzo, “MYC and prostate cancer,” Genes and Cancer, vol. 1, no. 6, pp. 617–628, 2010. View at Publisher · View at Google Scholar · View at Scopus
  249. J. P. Alao, “The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention,” Molecular Cancer, vol. 6, article 24, 2007. View at Publisher · View at Google Scholar · View at Scopus
  250. T. Grigoryan, P. Wend, A. Klaus, and W. Birchmeier, “Deciphering the function of canonical Wnt signals in development and disease: conditional loss- and gain-of-function mutations of β-catenin in mice,” Genes and Development, vol. 22, no. 17, pp. 2308–2341, 2008. View at Publisher · View at Google Scholar · View at Scopus
  251. C. L. Hall, A. Bafico, J. Dai, S. A. Aaronson, and E. T. Keller, “Prostate cancer cells promote osteoblastic bone metastases through Wnts,” Cancer Research, vol. 65, no. 17, pp. 7554–7560, 2005. View at Publisher · View at Google Scholar · View at Scopus
  252. K. J. Bruxvoort, H. M. Charbonneau, T. A. Giambernardi et al., “Inactivation of Apc in the mouse prostate causes prostate carcinoma,” Cancer Research, vol. 67, no. 6, pp. 2490–2496, 2007. View at Publisher · View at Google Scholar · View at Scopus
  253. P. Uysal-Onganer, Y. Kawano, M. Caro et al., “Wnt-11 promotes neuroendocrine-like differentiation, survival and migration of prostate cancer cells,” Molecular Cancer, vol. 9, article 55, 2010. View at Publisher · View at Google Scholar · View at Scopus
  254. S. Gupta, K. Iljin, H. Sara et al., “FZD4 as a mediator of ERG oncogene-induced WNT signaling and epithelial-to-mesenchymal transition in human prostate cancer cells,” Cancer Research, vol. 70, no. 17, pp. 6735–6745, 2010. View at Publisher · View at Google Scholar · View at Scopus
  255. M. A. Liss, M. Schlicht, A. Kahler et al., “Characterization of soy-based changes in Wnt-frizzled signaling in prostate cancer,” Cancer Genomics and Proteomics, vol. 7, no. 5, pp. 245–252, 2010. View at Scopus
  256. D. R. Chesire and W. B. Isaacs, “β-Catenin signaling in prostate cancer: an early perspective,” Endocrine-Related Cancer, vol. 10, no. 4, pp. 537–560, 2003. View at Publisher · View at Google Scholar · View at Scopus
  257. B. He, L. You, K. Uematsu et al., “A monoclonal antibody against Wnt-1 induces apoptosis in human cancer cells,” Neoplasia, vol. 6, no. 1, pp. 7–14, 2004. View at Scopus
  258. G. W. Yardy and S. F. Brewster, “Wnt signalling and prostate cancer,” Prostate Cancer and Prostatic Diseases, vol. 8, no. 2, pp. 119–126, 2005. View at Publisher · View at Google Scholar · View at Scopus
  259. S. Le Guellec, I. Soubeyran, P. Rochaix et al., “CTNNB1 mutation analysis is a useful tool for the diagnosis of desmoid tumors: a study of 260 desmoid tumors and 191 potential morphologic mimics,” Modern Pathology, vol. 25, pp. 1551–1558, 2012.
  260. K. Willert, J. D. Brown, E. Danenberg et al., “Wnt proteins are lipid-modified and can act as stem cell growth factors,” Nature, vol. 423, no. 6938, pp. 448–452, 2003. View at Publisher · View at Google Scholar · View at Scopus
  261. M. Sharma, W. W. Chuang, and Z. Sun, “Phosphatidylinositol 3-kinase/Akt stimulates androgen pathway through GSK3β inhibition and nuclear β-catenin accumulation,” Journal of Biological Chemistry, vol. 277, no. 34, pp. 30935–30941, 2002. View at Publisher · View at Google Scholar · View at Scopus
  262. P. Polakis, “The many ways of Wnt in cancer,” Current Opinion in Genetics and Development, vol. 17, no. 1, pp. 45–51, 2007. View at Publisher · View at Google Scholar · View at Scopus
  263. P. Wend, J. D. Holland, U. Ziebold, and W. Birchmeier, “Wnt signaling in stem and cancer stem cells,” Seminars in Cell and Developmental Biology, vol. 21, no. 8, pp. 855–863, 2010. View at Publisher · View at Google Scholar · View at Scopus
  264. T. Reya, S. J. Morrison, M. F. Clarke, and I. L. Weissman, “Stem cells, cancer, and cancer stem cells,” Nature, vol. 414, no. 6859, pp. 105–111, 2001. View at Publisher · View at Google Scholar · View at Scopus
  265. M. D. Castellone, H. Teramoto, B. O. Williams, K. M. Druey, and J. S. Gutkind, “Medicine: prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-β-catenin signaling axis,” Science, vol. 310, no. 5753, pp. 1504–1510, 2005. View at Publisher · View at Google Scholar · View at Scopus
  266. M. Lepourcelet, Y. N. P. Chen, D. S. France et al., “Small-molecule antagonists of the oncogenic Tcf/β-catenin protein complex,” Cancer Cell, vol. 5, no. 1, pp. 91–102, 2004. View at Publisher · View at Google Scholar · View at Scopus
  267. J. P. Rey and D. L. Ellies, “Wnt modulators in the biotech pipeline,” Developmental Dynamics, vol. 239, no. 1, pp. 102–114, 2010. View at Publisher · View at Google Scholar · View at Scopus