Table of Contents
Journal of Signal Transduction
Volume 2015, Article ID 282567, 13 pages
http://dx.doi.org/10.1155/2015/282567
Review Article

Phosphatase and Tensin Homologue: Novel Regulation by Developmental Signaling

Department of Pharmacology and Toxicology, Indiana University School of Medicine, IU-Melvin and Bren Simon Cancer Center, Indianapolis, IN 46202, USA

Received 6 April 2015; Revised 6 June 2015; Accepted 1 July 2015

Academic Editor: Matthias Gaestel

Copyright © 2015 Travis J. Jerde. 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. Milella, I. Falcone, F. Conciatori et al., “PTEN: multiple functions in human malignant tumors,” Frontiers in Oncology, vol. 5, article 24, 2015. View at Google Scholar
  2. J.-O. Lee, H. Yang, M.-M. Georgescu et al., “Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association,” Cell, vol. 99, no. 3, pp. 323–334, 1999. View at Publisher · View at Google Scholar · View at Scopus
  3. W.-L. Yang, G. Jin, C.-F. Li et al., “Cycles of ubiquitination and deubiquitination critically regulate growth factor-mediated activation of Akt signaling,” Science Signaling, vol. 6, no. 257, article ra3, 2013. View at Publisher · View at Google Scholar · View at Scopus
  4. J. Gu, S. Nada, M. Okada, and K. Sekiguchi, “Csk regulates integrin-mediated signals: involvement of differential activation of ERK and Akt,” Biochemical and Biophysical Research Communications, vol. 303, no. 3, pp. 973–977, 2003. View at Publisher · View at Google Scholar · View at Scopus
  5. A. Clerk and P. H. Sugden, “Activation of protein kinase cascades in the heart by hypertrophic G protein-coupled receptor agonists,” The American Journal of Cardiology, vol. 83, no. 12, pp. 64H–69H, 1999. View at Google Scholar · View at Scopus
  6. I. Tonic, W.-N. Yu, Y. Park, C.-C. Chen, and N. Hay, “Akt activation emulates Chk1 inhibition and Bcl2 overexpression and abrogates G2 cell cycle checkpoint by inhibiting BRCA1 foci,” The Journal of Biological Chemistry, vol. 285, no. 31, pp. 23790–23798, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. S. Fatrai, L. Elghazi, N. Balcazar et al., “Akt induces β-cell proliferation by regulating cyclin D1, cyclin D2, and p21 levels and cyclin-dependent kinase-4 activity,” Diabetes, vol. 55, no. 2, pp. 318–325, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Aoki, E. Blazek, and P. K. Vogt, “A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 1, pp. 136–141, 2001. View at Publisher · View at Google Scholar · View at Scopus
  9. H. Guan, L. Song, J. Cai et al., “Sphingosine kinase 1 regulates the Akt/FOXO3a/Bim pathway and contributes to apoptosis resistance in glioma cells,” PLoS ONE, vol. 6, no. 5, Article ID e19946, 2011. View at Publisher · View at Google Scholar · View at Scopus
  10. T. D. Dung, C. H. Day, T. V. Binh et al., “PP2A mediates diosmin p53 activation to block HA22T cell proliferation and tumor growth in xenografted nude mice through PI3K-Akt-MDM2 signaling suppression,” Food and Chemical Toxicology, vol. 50, no. 5, pp. 1802–1810, 2012. View at Publisher · View at Google Scholar · View at Scopus
  11. K. Shanmugasundaram, K. Block, B. K. Nayak, C. B. Livi, M. A. Venkatachalam, and S. Sudarshan, “PI3K regulation of the SKP-2/p27 axis through mTORC2,” Oncogene, vol. 32, no. 16, pp. 2027–2036, 2013. View at Publisher · View at Google Scholar · View at Scopus
  12. J.-C. Chang, H.-H. Chang, C.-T. Lin, and S. J. Lo, “The integrin α6β1 modulation of PI3K and Cdc42 activities induces dynamic filopodium formation in human platelets,” Journal of Biomedical Science, vol. 12, no. 6, pp. 881–898, 2005. View at Publisher · View at Google Scholar · View at Scopus
  13. E. Hajduch, G. J. Litherland, and H. S. Hundal, “Protein kinase B (PKB/Akt)—a key regulator of glucose transport?” FEBS Letters, vol. 492, no. 3, pp. 199–203, 2001. View at Publisher · View at Google Scholar · View at Scopus
  14. M. M. Martin, J. A. Buckenberger, J. Jiang et al., “TGF-beta1 stimulates human at1 receptor expression in lung fibroblasts by cross talk between the Smad, p38 MAPK, JNK, and PI3K signaling pathways,” The American Journal of Physiology—Lung Cellular and Molecular Physiology, vol. 293, no. 3, pp. L790–L799, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. M. M. Martin, J. A. Buckenberger, J. Jiang et al., “TGF-β1 stimulates human at1 receptor expression in lung fibroblasts by cross talk between the Smad, p38 MAPK, JNK, and PI3K signaling pathways,” The American Journal of Physiology—Lung Cellular and Molecular Physiology, vol. 293, no. 3, pp. L790–L799, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. K. Abell and C. J. Watson, “The Jak/Stat pathway: a novel way to regulate PI3K activity,” Cell Cycle, vol. 4, no. 7, pp. 897–900, 2005. View at Publisher · View at Google Scholar · View at Scopus
  17. J.-Y. Hwang, R. S. Duncan, C. Madry, M. Singh, and P. Koulen, “Progesterone potentiates calcium release through IP3 receptors by an Akt-mediated mechanism in hippocampal neurons,” Cell Calcium, vol. 45, no. 3, pp. 233–242, 2009. View at Publisher · View at Google Scholar · View at Scopus
  18. G. Pappas, L. A. Zumstein, A. Munshi, M. Hobbs, and R. E. Meyn, “Adenoviral-mediated PTEN expression radiosensitizes non-small cell lung cancer cells by suppressing DNA repair capacity,” Cancer Gene Therapy, vol. 14, no. 6, pp. 543–549, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. 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
  20. J. Bloomekatz, J. Grego-Bessa, I. Migeotte, and K. V. Anderson, “Pten regulates collective cell migration during specification of the anterior-posterior axis of the mouse embryo,” Developmental Biology, vol. 364, no. 2, pp. 192–201, 2012. View at Publisher · View at Google Scholar · View at Scopus
  21. S. Ueno, R. Kono, and Y. Iwao, “PTEN is required for the normal progression of gastrulation by repressing cell proliferation after MBT in Xenopus embryos,” Developmental Biology, vol. 297, no. 1, pp. 274–283, 2006. View at Publisher · View at Google Scholar · View at Scopus
  22. C. B. Knobbe, A. Merlo, and G. Reifenberger, “Pten signaling in gliomas,” Neuro Oncology, vol. 4, pp. 196–211, 2002. View at Publisher · View at Google Scholar · View at Scopus
  23. E. Kirches, J. Steiner, T. Schneider et al., “Lhermitte-Duclos disease caused by a novel germline PTEN mutation R173P in a patient presenting with psychosis,” Neuropathology and Applied Neurobiology, vol. 36, no. 1, pp. 86–89, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. J.-I. Murata, M. Tada, Y. Sawamura, K. Mitsumori, H. Abe, and K. Nagashima, “Dysplastic gangliocytoma (Lhermitte-Duclos disease) associated with Cowden disease: report of a case and review of the literature for the genetic relationship between the two diseases,” Journal of Neuro-Oncology, vol. 41, no. 2, pp. 129–136, 1999. View at Publisher · View at Google Scholar · View at Scopus
  25. G. Zhu, L. M. L. Chow, I. T. Bayazitov et al., “Pten deletion causes mTorc1-dependent ectopic neuroblast differentiation without causing uniform migration defects,” Development, vol. 139, no. 18, pp. 3422–3431, 2012. View at Publisher · View at Google Scholar · View at Scopus
  26. K. L. McBride, E. A. Varga, M. T. Pastore et al., “Confirmation study of PTEN mutations among individuals with autism or developmental delays/mental retardation and macrocephaly,” Autism Research, vol. 3, no. 3, pp. 137–141, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. J. Zhou and L. F. Parada, “PTEN signaling in autism spectrum disorders,” Current Opinion in Neurobiology, vol. 22, no. 5, pp. 873–879, 2012. View at Publisher · View at Google Scholar · View at Scopus
  28. S. A. Backman, V. Stambolic, A. Suzuki et al., “Deletion of Pten in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte-Duclos disease,” Nature Genetics, vol. 29, no. 4, pp. 396–403, 2001. View at Publisher · View at Google Scholar · View at Scopus
  29. L. Cotter, M. Ozçelik, C. Jacob et al., “Dlg1-PTEN interaction regulates myelin thickness to prevent damaging peripheral nerve overmyelination,” Science, vol. 328, no. 5984, pp. 1415–1418, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. S. Ogawa, C.-H. Kwon, J. Zhou, D. Koovakkattu, L. F. Parada, and C. M. Sinton, “A seizure-prone phenotype is associated with altered free-running rhythm in Pten mutant mice,” Brain Research, vol. 1168, no. 1, pp. 112–123, 2007. View at Publisher · View at Google Scholar · View at Scopus
  31. C.-H. Kwon, X. Zhu, J. Zhang, and S. J. Baker, “mTor is required for hypertrophy of Pten-deficient neuronal soma in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 22, pp. 12923–12928, 2003. View at Publisher · View at Google Scholar · View at Scopus
  32. C.-H. Kwon, B. W. Luikart, C. M. Powell et al., “Pten regulates neuronal arborization and social interaction in mice,” Neuron, vol. 50, no. 3, pp. 377–388, 2006. View at Publisher · View at Google Scholar · View at Scopus
  33. A. Suzuki, S. Itami, M. Ohishi et al., “Keratinocyte-specific Pten deficiency results in epidermal hyperplasia, accelerated hair follicle morphogenesis and tumor formation,” Cancer Research, vol. 63, no. 3, pp. 674–681, 2003. View at Google Scholar · View at Scopus
  34. T. Inoue-Narita, K. Hamada, T. Sasaki et al., “Pten deficiency in melanocytes results in resistance to hair graying and susceptibility to carcinogen-induced melanomagenesis,” Cancer Research, vol. 68, no. 14, pp. 5760–5768, 2008. View at Publisher · View at Google Scholar · View at Scopus
  35. R. K. Patel and C. Mohan, “PI3K/AKT signaling and systemic autoimmunity,” Immunologic Research, vol. 31, no. 1, pp. 47–55, 2005. View at Publisher · View at Google Scholar · View at Scopus
  36. K. Podsypanina, L. H. Ellenson, A. Nemes et al., “Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 4, pp. 1563–1568, 1999. View at Publisher · View at Google Scholar · View at Scopus
  37. M. Kashiwada, P. Lu, and P. B. Rothman, “PIP3 pathway in regulatory T cells and autoimmunity,” Immunologic Research, vol. 39, no. 1–3, pp. 194–224, 2007. View at Publisher · View at Google Scholar · View at Scopus
  38. A. Suzuki, M. T. Yamaguchi, T. Ohteki et al., “T cell-specific loss of Pten leads to defects in central and peripheral tolerance,” Immunity, vol. 14, no. 5, pp. 523–534, 2001. View at Publisher · View at Google Scholar · View at Scopus
  39. Y. Yamanaka, H. Tagawa, N. Takahashi et al., “Aberrant overexpression of microRNAs activate AKT signaling via down-regulation of tumor suppressors in natural killer-cell lymphoma/leukemia,” Blood, vol. 114, no. 15, pp. 3265–3275, 2009. View at Publisher · View at Google Scholar · View at Scopus
  40. H. Kishimoto, T. Ohteki, N. Yajima et al., “The Pten/PI3K pathway governs the homeostasis of Vα14iNKT cells,” Blood, vol. 109, no. 8, pp. 3316–3324, 2007. View at Publisher · View at Google Scholar · View at Scopus
  41. A. Suzuki, T. Kaisho, M. Ohishi et al., “Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination,” Journal of Experimental Medicine, vol. 197, no. 5, pp. 657–667, 2003. View at Publisher · View at Google Scholar · View at Scopus
  42. M. Nishio, K.-I. Watanabe, J. Sasaki et al., “Control of cell polarity and motility by the PtdIns(3,4,5)P3 phosphatase SHIP1,” Nature Cell Biology, vol. 9, no. 1, pp. 36–44, 2007. View at Publisher · View at Google Scholar · View at Scopus
  43. S. Kuroda, M. Nishio, T. Sasaki et al., “Effective clearance of intracellular Leishmania major in vivo requires Pten in macrophages,” European Journal of Immunology, vol. 38, no. 5, pp. 1331–1340, 2008. View at Publisher · View at Google Scholar · View at Scopus
  44. Ö. H. Yilmaz, R. Valdez, B. K. Theisen et al., “Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells,” Nature, vol. 441, no. 7092, pp. 475–482, 2006. View at Publisher · View at Google Scholar · View at Scopus
  45. Y. Li, K. Podsypanina, X. Liu et al., “Deficiency of Pten accelerates mammary oncogenesis in MMTV-Wnt-1 transgenic mice,” BMC Molecular Biology, vol. 2, article 2, 2001. View at Publisher · View at Google Scholar · View at Scopus
  46. P. Reddy, L. Liu, D. Adhikari et al., “Oocyte-specific deletion of pten causes premature activation of the primordial follicle pool,” Science, vol. 319, no. 5863, pp. 611–613, 2008. View at Publisher · View at Google Scholar · View at Scopus
  47. H. Tsuruta, H. Kishimoto, T. Sasaki et al., “Hyperplasia and carcinomas in Pten-deficient mice and reduced PTEN protein in human bladder cancer patients,” Cancer Research, vol. 66, no. 17, pp. 8389–8396, 2006. View at Publisher · View at Google Scholar · View at Scopus
  48. L. I. Yoo, D. W. Liu, S. Le Vu, R. T. Bronson, H. Wu, and J. Yuan, “Pten deficiency activates distinct downstream signaling pathways in a tissue-specific manner,” Cancer Research, vol. 66, no. 4, pp. 1929–1939, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. J. Li, C. Yen, D. Liaw et al., “PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer,” Science, vol. 275, no. 5308, pp. 1943–1947, 1997. View at Publisher · View at Google Scholar · View at Scopus
  50. N. D. Deocampo, H. Huang, and D. J. Tindall, “The role of PTEN in the progression and survival of prostate cancer,” Minerva Endocrinologica, vol. 28, no. 2, pp. 145–153, 2003. View at Google Scholar · View at Scopus
  51. S. A. Backman, D. Ghazarian, K. So et al., “Early onset of neoplasia in the prostate and skin of mice with tissue-specific deletion of Pten,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 6, pp. 1725–1730, 2004. View at Publisher · View at Google Scholar · View at Scopus
  52. X. Wu, K. Xu, L. Zhang et al., “Differentiation of the ductal epithelium and smooth muscle in the prostate gland are regulated by the Notch/PTEN-dependent mechanism,” Developmental Biology, vol. 356, no. 2, pp. 337–349, 2011. View at Publisher · View at Google Scholar · View at Scopus
  53. D. Kim and G. R. Dressler, “PTEN modulates GDNF/RET mediated chemotaxis and branching morphogenesis in the developing kidney,” Developmental Biology, vol. 307, no. 2, pp. 290–299, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. N. O. Lindström, M. L. Lawrence, S. F. Burn et al., “Integrated β-catenin, BMP, PTEN, and notch signalling patterns the nephron,” eLife, no. 4, Article ID e04000, 2015. View at Publisher · View at Google Scholar · View at Scopus
  55. V. Marsh, D. J. Winton, G. T. Williams et al., “Epithelial Pten is dispensable for intestinal homeostasis but suppresses adenoma development and progression after Apc mutation,” Nature Genetics, vol. 40, no. 12, pp. 1436–1444, 2008. View at Publisher · View at Google Scholar · View at Scopus
  56. S. Matsuda, M. Kobayashi, and Y. Kitagishi, “Roles for PI3K/AKT/PTEN pathway in cell signaling of nonalcoholic fatty liver disease,” ISRN Endocrinology, vol. 2013, Article ID 472432, 7 pages, 2013. View at Publisher · View at Google Scholar
  57. X. Qi, J. Xu, P. Gu, X. Yang, and X. Gao, “PTEN in smooth muscle cells is essential for colonic immune homeostasis,” International Journal of Biochemistry and Cell Biology, vol. 53, pp. 108–114, 2014. View at Publisher · View at Google Scholar · View at Scopus
  58. A. Pal, T. M. Barber, M. Van de Bunt et al., “PTEN mutations as a cause of constitutive insulin sensitivity and obesity,” The New England Journal of Medicine, vol. 367, no. 11, pp. 1002–1011, 2012. View at Publisher · View at Google Scholar · View at Scopus
  59. B. L. Stiles, C. Kuralwalla-Martinez, W. Guo et al., “Selective deletion of Pten in pancreatic β cells leads to increased islet mass and resistance to STZ-induced diabetes,” Molecular and Cellular Biology, vol. 26, no. 7, pp. 2772–2781, 2006. View at Publisher · View at Google Scholar · View at Scopus
  60. L. Wang, C. T. Luk, E. P. Cai et al., “PTEN deletion in pancreatic α-cells protects against high-fat diet-induced hyperglucagonemia and insulin resistance,” Diabetes, vol. 64, no. 1, pp. 147–157, 2015. View at Publisher · View at Google Scholar · View at Scopus
  61. C. Kurlawalla-Martinez, B. Stiles, Y. Wang, S. U. Devaskar, B. B. Kahn, and H. Wu, “Insulin hypersensitivity and resistance to streptozotocin-induced diabetes in mice lacking PTEN in adipose tissue,” Molecular and Cellular Biology, vol. 25, no. 6, pp. 2498–2510, 2005. View at Publisher · View at Google Scholar · View at Scopus
  62. N. Wijesekara, D. Konrad, M. Eweida et al., “Muscle-specific Pten deletion protects against insulin resistance and diabetes,” Molecular and Cellular Biology, vol. 25, no. 3, pp. 1135–1145, 2005. View at Publisher · View at Google Scholar · View at Scopus
  63. K. Hamada, T. Sasaki, P. A. Koni et al., “The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis,” Genes and Development, vol. 19, no. 17, pp. 2054–2065, 2005. View at Publisher · View at Google Scholar · View at Scopus
  64. N. D. Roe, X. Xu, M. R. Kandadi et al., “Targeted deletion of PTEN in cardiomyocytes renders cardiac contractile dysfunction through interruption of Pink1-AMPK signaling and autophagy,” Biochimica et Biophysica Acta: Molecular Basis of Disease, vol. 1852, no. 2, pp. 290–298, 2015. View at Publisher · View at Google Scholar · View at Scopus
  65. A. F. Ford-Hutchinson, Z. Ali, S. E. Lines, B. Hallgrímsson, S. K. Boyd, and F. R. Jirik, “Inactivation of Pten in osteo-chondroprogenitor cells leads to epiphyseal growth plate abnormalities and skeletal overgrowth,” Journal of Bone and Mineral Research, vol. 22, no. 8, pp. 1245–1259, 2007. View at Publisher · View at Google Scholar · View at Scopus
  66. T. A. Burgers, M. F. Hoffmann, C. J. Collins et al., “Mice lacking pten in osteoblasts have improved intramembranous and late endochondral fracture healing,” PLoS ONE, vol. 8, no. 5, Article ID e63857, 2013. View at Publisher · View at Google Scholar · View at Scopus
  67. N. R. Leslie, L. Spinelli, P. Tibarewal et al., “Indirect mechanisms of carcinogenesis via downregulation of PTEN function,” Advances in Enzyme Regulation, vol. 50, no. 1, pp. 112–118, 2010. View at Publisher · View at Google Scholar · View at Scopus
  68. L. He, “Posttranscriptional regulation of PTEN dosage by noncoding RNAs,” Science Signaling, vol. 3, no. 146, article pe39, 2010. View at Publisher · View at Google Scholar · View at Scopus
  69. F. Vazquez, S. R. Grossman, Y. Takahashi, M. V. Rokas, N. Nakamura, and W. R. Sellers, “Phosphorylation of the PTEN tail acts as an inhibitory switch by preventing its recruitment into a protein complex,” The Journal of Biological Chemistry, vol. 276, no. 52, pp. 48627–48630, 2001. View at Publisher · View at Google Scholar · View at Scopus
  70. X. Wang, L. C. Trotman, T. Koppie et al., “NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN,” Cell, vol. 128, no. 1, pp. 129–139, 2007. View at Publisher · View at Google Scholar · View at Scopus
  71. N. R. Leslie and M. Foti, “Non-genomic loss of PTEN function in cancer: not in my genes,” Trends in Pharmacological Sciences, vol. 32, no. 3, pp. 131–140, 2011. View at Publisher · View at Google Scholar · View at Scopus
  72. Y. Xing, C. Li, L. Hu et al., “Mechanisms of TGFβ inhibition of LUNG endodermal morphogenesis: the role of TβRII, Smads, Nkx2.1 and Pten,” Developmental Biology, vol. 320, no. 2, pp. 340–350, 2008. View at Publisher · View at Google Scholar · View at Scopus
  73. J. P. Luyendyk, G. A. Schabbauer, M. Tencati, T. Holscher, R. Pawlinski, and N. Mackman, “Genetic analysis of the role of the PI3K-Akt pathway in lipopolysaccharide-induced cytokine and tissue factor gene expression in monocytes/macrophages,” Journal of Immunology, vol. 180, no. 6, pp. 4218–4226, 2008. View at Publisher · View at Google Scholar · View at Scopus
  74. F. Sun, K. K. Park, S. Belin et al., “Sustained axon regeneration induced by co-deletion of PTEN and SOCS3,” Nature, vol. 480, no. 7377, pp. 372–375, 2011. View at Publisher · View at Google Scholar · View at Scopus
  75. C. B. Knobbe, V. Lapin, A. Suzuki, and T. W. Mak, “The roles of PTEN in development, physiology and tumorigenesis in mouse models: a tissue-by-tissue survey,” Oncogene, vol. 27, no. 41, pp. 5398–5415, 2008. View at Publisher · View at Google Scholar · View at Scopus
  76. S. J. Assinder, Q. Dong, Z. Kovacevic, and D. R. Richardson, “The TGF-beta, PI3K/Akt and PTEN pathways: established and proposed biochemical integration in prostate cancer,” Biochemical Journal, vol. 417, no. 2, pp. 411–421, 2009. View at Publisher · View at Google Scholar · View at Scopus
  77. K. A. Waite and C. Eng, “From developmental disorder to heritable cancer: it's all in the BMP/TGF-β family,” Nature Reviews Genetics, vol. 4, no. 10, pp. 763–773, 2003. View at Publisher · View at Google Scholar · View at Scopus
  78. H. B. Newton, “Molecular neuro-oncology and development of targeted therapeutic strategies for brain tumors. Part 2: PI3K/Akt/PTEN, mTOR, SHH/PTCH and angiogenesis,” Expert Review of Anticancer Therapy, vol. 4, no. 1, pp. 105–128, 2004. View at Publisher · View at Google Scholar · View at Scopus
  79. R. H. Kim, M. Peters, Y. Jang et al., “DJ-1, a novel regulator of the tumor suppressor PTEN,” Cancer Cell, vol. 7, no. 3, pp. 263–273, 2005. View at Publisher · View at Google Scholar · View at Scopus
  80. J. Lu, H. W. Jeong, N. Kong et al., “Stem cell factor SALL4 represses the transcriptions of PTEN and SALL1 through an epigenetic repressor complex,” PLoS ONE, vol. 4, no. 5, Article ID e5577, 2009. View at Publisher · View at Google Scholar · View at Scopus
  81. M. M. A. Rizvi, M. S. Alam, A. Ali, S. J. Mehdi, S. Batra, and A. K. Mandal, “Aberrant promoter methylation and inactivation of PTEN gene in cervical carcinoma from Indian population,” Journal of Cancer Research and Clinical Oncology, vol. 137, no. 8, pp. 1255–1262, 2011. View at Publisher · View at Google Scholar · View at Scopus
  82. J. Liu, “Control of protein synthesis and mRNA degradation by microRNAs,” Current Opinion in Cell Biology, vol. 20, no. 2, pp. 214–221, 2008. View at Publisher · View at Google Scholar · View at Scopus
  83. S. W. Shan, L. Fang, T. Shatseva et al., “Mature miR-17-5p and passenger miR-17-3p induce hepatocellular carcinoma by targeting PTEN, GalNT7 and vimentin in different signal pathways,” Journal of Cell Science, vol. 126, part 6, pp. 1517–1530, 2013. View at Publisher · View at Google Scholar · View at Scopus
  84. Z. Liang, Y. Li, K. Huang, N. Wagar, and H. Shim, “Regulation of miR-19 to breast cancer chemoresistance through targeting PTEN,” Pharmaceutical Research, vol. 28, no. 12, pp. 3091–3100, 2011. View at Publisher · View at Google Scholar · View at Scopus
  85. X. Lu, Q. Fan, L. Xu et al., “Ursolic acid attenuates diabetic mesangial cell injury through the up-regulation of autophagy via miRNA-21/PTEN/Akt/mTOR suppression,” PLoS ONE, vol. 10, no. 2, Article ID e0117400, 2015. View at Publisher · View at Google Scholar
  86. L. Poliseno, L. Salmena, J. Zhang, B. Carver, W. J. Haveman, and P. P. Pandolfi, “A coding-independent function of gene and pseudogene mRNAs regulates tumour biology,” Nature, vol. 465, no. 7301, pp. 1033–1038, 2010. View at Publisher · View at Google Scholar · View at Scopus
  87. Y. Tay, L. Kats, L. Salmena et al., “Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs,” Cell, vol. 147, no. 2, pp. 344–357, 2011. View at Publisher · View at Google Scholar · View at Scopus
  88. L. Odriozola, G. Singh, T. Hoang, and A. M. Chan, “Regulation of PTEN activity by its carboxyl-terminal autoinhibitory domain,” The Journal of Biological Chemistry, vol. 282, no. 32, pp. 23306–23315, 2007. View at Publisher · View at Google Scholar · View at Scopus
  89. Z. Li, X. Dong, Z. Wang et al., “Regulation of PTEN by Rho small GTPases,” Nature Cell Biology, vol. 7, no. 4, pp. 399–404, 2005. View at Publisher · View at Google Scholar · View at Scopus
  90. E.-K. Yim, G. Peng, H. Dai et al., “Rak functions as a tumor suppressor by regulating PTEN protein stability and function,” Cancer Cell, vol. 15, no. 4, pp. 304–314, 2009. View at Publisher · View at Google Scholar · View at Scopus
  91. A. M. Al-Khouri, Y. Ma, S. H. Togo, S. Williams, and T. Mustelin, “Cooperative phosphorylation of the tumor suppressor phosphatase and tensin homologue (PTEN) by casein kinases and glycogen synthase kinase 3β,” The Journal of Biological Chemistry, vol. 280, no. 42, pp. 35195–35202, 2005. View at Publisher · View at Google Scholar · View at Scopus
  92. H. Maccario, N. M. Perera, L. Davidson, C. P. Downes, and N. R. Leslie, “PTEN is destabilized by phosphorylation on Thr366,” Biochemical Journal, vol. 405, no. 3, pp. 439–444, 2007. View at Publisher · View at Google Scholar · View at Scopus
  93. K. A. Waite and C. Eng, “BMP2 exposure results in decreased PTEN protein degradation and increased PTEN levels,” Human Molecular Genetics, vol. 12, no. 6, pp. 679–684, 2003. View at Publisher · View at Google Scholar · View at Scopus
  94. T. J. Jerde, Z. Wu, D. Theodorescu, and W. Bushman, “Regulation of phosphatase homologue of tensin protein expression by bone morphogenetic proteins in prostate epithelial cells,” Prostate, vol. 71, no. 8, pp. 791–800, 2011. View at Publisher · View at Google Scholar · View at Scopus
  95. G. Singh and A. M. Chan, “Post-translational modifications of PTEN and their potential therapeutic implications,” Current Cancer Drug Targets, vol. 11, no. 5, pp. 536–547, 2011. View at Publisher · View at Google Scholar · View at Scopus
  96. T. Ikenoue, K. Inoki, B. Zhao, and K.-L. Guan, “PTEN acetylation modulates its interaction with PDZ domain,” Cancer Research, vol. 68, no. 17, pp. 6908–6912, 2008. View at Publisher · View at Google Scholar · View at Scopus
  97. L. C. Trotman, X. Wang, A. Alimonti et al., “Ubiquitination regulates PTEN nuclear import and tumor suppression,” Cell, vol. 128, no. 1, pp. 141–156, 2007. View at Publisher · View at Google Scholar · View at Scopus
  98. T. Tolkacheva, M. Boddapati, A. Sanfiz, K. Tsuchida, A. C. Kimmelman, and A. M.-L. Chan, “Regulation of PTEN binding to MAGI-2 by two putative phosphorylation sites at threonine 382 and 383,” Cancer Research, vol. 61, no. 13, pp. 4985–4989, 2001. View at Google Scholar · View at Scopus
  99. E. Lima-Fernandes, H. Enslen, E. Camand et al., “Distinct functional outputs of PTEN signalling are controlled by dynamic association with β-arrestins,” The EMBO Journal, vol. 30, no. 13, pp. 2557–2568, 2011. View at Publisher · View at Google Scholar · View at Scopus
  100. M. T. van Diepen, M. Parsons, C. P. Downes, N. R. Leslie, R. Hindges, and B. J. Eickholt, “MyosinV controls PTEN function and neuronal cell size,” Nature Cell Biology, vol. 11, no. 10, pp. 1191–1196, 2009. View at Publisher · View at Google Scholar · View at Scopus
  101. R. B. Chagpar, P. H. Links, M. C. Pastor et al., “Direct positive regulation of PTEN by the p85 subunit of phosphatidylinositol 3-kinase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 12, pp. 5471–5476, 2010. View at Publisher · View at Google Scholar · View at Scopus
  102. Y. Takahashi, F. C. Morales, E. L. Kreimann, and M.-M. Georgescu, “PTEN tumor suppressor associates with NHERF proteins to attenuate PDGF receptor signaling,” The EMBO Journal, vol. 25, no. 4, pp. 910–920, 2006. View at Publisher · View at Google Scholar · View at Scopus
  103. M. Valiente, A. Andrés-Pons, B. Gomar et al., “Binding of PTEN to specific PDZ domains contributes to PTEN protein stability and phosphorylation by microtubule-associated serine/threonine kinases,” The Journal of Biological Chemistry, vol. 280, no. 32, pp. 28936–28943, 2005. View at Publisher · View at Google Scholar · View at Scopus
  104. S. Quintes, S. Goebbels, G. Saher, M. H. Schwab, and K.-A. Nave, “Neuron-glia signaling and the protection of axon function by Schwann cells,” Journal of the Peripheral Nervous System, vol. 15, no. 1, pp. 10–16, 2010. View at Publisher · View at Google Scholar · View at Scopus
  105. B. Fine, C. Hodakoski, S. Koujak et al., “Activation of the PI3K pathway in cancer through inhibition of PTEN by exchange factor P-REX2a,” Science, vol. 325, no. 5945, pp. 1261–1265, 2009. View at Publisher · View at Google Scholar · View at Scopus
  106. L. He, A. Ingram, A. P. Rybak, and D. Tang, “Shank-interacting protein-like 1 promotes tumorigenesis via PTEN inhibition in human tumor cells,” The Journal of Clinical Investigation, vol. 120, no. 6, pp. 2094–2108, 2010. View at Publisher · View at Google Scholar · View at Scopus
  107. L. He, C. Fan, A. Kapoor et al., “α-Mannosidase 2C1 attenuates PTEN function in prostate cancer cells,” Nature Communications, vol. 2, no. 1, article 307, 2011. View at Publisher · View at Google Scholar · View at Scopus
  108. Z. Radisavljevic, “AKT as locus of cancer positive feedback loops and extreme robustness,” Journal of Cellular Physiology, vol. 228, no. 3, pp. 522–524, 2013. View at Publisher · View at Google Scholar · View at Scopus
  109. M. Y. Lee, H. W. Lim, S. H. Lee, and H. J. Han, “Smad, PI3K/Akt, and wnt-dependent signaling pathways are involved in BMP-4-induced ESC self-renewal,” Stem Cells, vol. 27, no. 8, pp. 1858–1868, 2009. View at Publisher · View at Google Scholar · View at Scopus
  110. K. Song, S. C. Cornelius, M. Reiss, and D. Danielpour, “Insulin-like growth factor-I inhibits transcriptional responses of transforming growth factor-β by phosphatidylinositol 3-kinase/Akt-dependent suppression of the activation of Smad3 but not Smad2,” The Journal of Biological Chemistry, vol. 278, no. 40, pp. 38342–38351, 2003. View at Publisher · View at Google Scholar · View at Scopus
  111. D. Fang, D. Hawke, Y. Zheng et al., “Phosphorylation of β-catenin by AKT promotes β-catenin transcriptional activity,” The Journal of Biological Chemistry, vol. 282, no. 15, pp. 11221–11229, 2007. View at Publisher · View at Google Scholar · View at Scopus
  112. Q. Lei, J. Jiao, L. Xin et al., “NKX3.1 stabilizes p53, inhibits AKT activation, and blocks prostate cancer initiation caused by PTEN loss,” Cancer Cell, vol. 9, no. 5, pp. 367–378, 2006. View at Publisher · View at Google Scholar · View at Scopus
  113. A. Sengupta, J. D. Molkentin, J.-H. Paik, R. A. DePinho, and K. E. Yutzey, “FoxO transcription factors promote cardiomyocyte survival upon induction of oxidative stress,” The Journal of Biological Chemistry, vol. 286, no. 9, pp. 7468–7478, 2011. View at Publisher · View at Google Scholar · View at Scopus
  114. C. H. M. Jamieson, L. E. Ailles, S. J. Dylla et al., “Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML,” The New England Journal of Medicine, vol. 351, no. 7, pp. 657–667, 2004. View at Publisher · View at Google Scholar · View at Scopus
  115. A. Androutsellis-Theotokis, R. R. Leker, F. Soldner et al., “Notch signalling regulates stem cell numbers in vitro and in vivo,” Nature, vol. 442, no. 7104, pp. 823–826, 2006. View at Publisher · View at Google Scholar · View at Scopus