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International Journal of Cell Biology
Volume 2012 (2012), Article ID 379685, 10 pages
http://dx.doi.org/10.1155/2012/379685
Review Article

Nongenomic Mechanisms of PTEN Regulation

1Department of Biology, College of Staten Island, 2800 Victory Boulevard, Staten Island, NY 10314, USA
2Biology Doctoral Program, City University of New York Graduate Center, 365 Fifth Avenue, New York, NY 10016, USA
3Biochemistry Doctoral Program, City University of New York Graduate Center, 365 Fifth Avenue, New York, NY 10016, USA
4BIOARRAY Therapeutics Inc., Venture Development Center, UMASS, 100 Morrissey Boulevard, Boston, MA 02125, USA

Received 2 November 2011; Revised 16 January 2012; Accepted 17 January 2012

Academic Editor: Andre Van Wijnen

Copyright © 2012 Jimmie E. Fata 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. 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
  2. P. A. Steck, M. A. Pershouse, S. A. Jasser et al., “Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers,” Nature Genetics, vol. 15, no. 4, pp. 356–362, 1997. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. D. M. Li and H. Sun, “TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor β,” Cancer Research, vol. 57, no. 11, pp. 2124–2129, 1997. View at Scopus
  4. S. J. Leevers, B. Vanhaesebroeck, and M. D. Waterfield, “Signalling through phosphoinositide 3-kinases: the lipids take centre stage,” Current Opinion in Cell Biology, vol. 11, no. 2, pp. 219–225, 1999. View at Publisher · View at Google Scholar · View at Scopus
  5. T. Maehama and J. E. Dixon, “The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate,” Journal of Biological Chemistry, vol. 273, no. 22, pp. 13375–13378, 1998. View at Publisher · View at Google Scholar · View at Scopus
  6. P. L. M. Dahia, “PTEN, a unique tumor suppressor gene,” Endocrine-Related Cancer, vol. 7, no. 2, pp. 115–129, 2000. View at Scopus
  7. A. Hlobilková, J. Knillová, J. Bártek, J. Lukás, and Z. Kolár, “The mechanism of action of the tumour suppressor gene PTEN,” Biomedical papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia, vol. 147, no. 1, pp. 19–25, 2003.
  8. S. Zhang and D. Yu, “PI(3)king apart PTEN's role in cancer,” Clinical Cancer Research, vol. 16, no. 17, pp. 4325–4330, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  9. V. Stambolic, A. Suzuki, J. L. De la Pompa et al., “Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN,” Cell, vol. 95, no. 1, pp. 29–39, 1998. View at Publisher · View at Google Scholar · View at Scopus
  10. H. Sun, R. Lesche, D. M. Li et al., “PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 11, pp. 6199–6204, 1999. View at Publisher · View at Google Scholar · View at Scopus
  11. C. Blanco-Aparicio, O. Renner, J. F. M. Leal, and A. Carnero, “PTEN, more than the AKT pathway,” Carcinogenesis, vol. 28, no. 7, pp. 1379–1386, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  12. M. M. Georgescu, K. H. Kirsch, P. Kaloudis, H. Yang, N. P. Pavletich, and H. Hanafusa, “Stabilization and productive positioning roles of the C2 domain of PTEN tumor suppressor,” Cancer Research, vol. 60, no. 24, pp. 7033–7038, 2000. View at Scopus
  13. J. J. Gildea, M. Herlevsen, M. A. Harding et al., “PTEN can inhibit in vitro organotypic and in vivo orthotopic invasion of human bladder cancer cells even in the absence of its lipid phosphatase activity,” Oncogene, vol. 23, no. 40, pp. 6788–6797, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. D. Koul, S. A. Jasser, Y. Lu et al., “Motif analysis of the tumor suppressor gene MMAC/PTEN identifies tyrosines critical for tumor suppression and lipid phosphatase activity,” Oncogene, vol. 21, no. 15, pp. 2357–2364, 2002. View at Publisher · View at Google Scholar · View at Scopus
  15. D. Maier, G. Jones, X. Li et al., “The PTEN lipid phosphatase domain is not required to inhibit invasion of glioma cells,” Cancer Research, vol. 59, no. 21, pp. 5479–5482, 1999. View at Scopus
  16. M. L. Sulis and R. Parsons, “PTEN: from pathology to biology,” Trends in Cell Biology, vol. 13, no. 9, pp. 478–483, 2003. View at Publisher · View at Google Scholar · View at Scopus
  17. L. P. Weng, J. L. Brown, and C. Eng, “PTEN induces apoptosis and cell cycle arrest through phosphoinositol-3-kinase/Akt-dependent and -independent pathways,” Human Molecular Genetics, vol. 10, no. 3, pp. 237–242, 2001. View at Scopus
  18. A. Radu, V. Neubauer, T. Akagi, H. Hanafusa, and M. M. Georgescu, “PTEN induces cell cycle arrest by decreasing the level and nuclear localization of cyclin D1,” Molecular and Cellular Biology, vol. 23, no. 17, pp. 6139–6149, 2003. View at Publisher · View at Google Scholar · View at Scopus
  19. F. B. Furnari, H. J. Su Huang, and W. K. Cavenee, “The phosphoinositol phosphatase activity of PTEN mediates a serum- sensitive G1 growth arrest in glioma cells,” Cancer Research, vol. 58, no. 22, pp. 5002–5008, 1998. View at Scopus
  20. M. Tamura, J. Gu, K. Matsumoto, S. I. Aota, R. Parsons, and K. M. Yamada, “Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN,” Science, vol. 280, no. 5369, pp. 1614–1617, 1998. View at Publisher · View at Google Scholar · View at Scopus
  21. M. Tamura, J. Gu, E. H. J. Danen, T. Takino, S. Miyamoto, and K. M. Yamada, “PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3-kinase/Akt cell survival pathway,” Journal of Biological Chemistry, vol. 274, no. 29, pp. 20693–20703, 1999. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Tamura, J. Gu, T. Takino, and K. M. Yamada, “Tumor suppressor PTEN inhibition of cell invasion, migration, and growth: differential involvement of focal adhesion kinase and p130(Cas),” Cancer Research, vol. 59, no. 2, pp. 442–449, 1999. View at Scopus
  23. M. Tamura, J. Gu, H. Tran, and K. M. Yamada, “PTEN gene and integrin signaling in cancer,” Journal of the National Cancer Institute, vol. 91, no. 21, pp. 1820–1828, 1999. View at Scopus
  24. J. A. Hobert and C. Eng, “PTEN hamartoma tumor syndrome: an overview,” Genetics in Medicine, vol. 11, no. 10, pp. 687–694, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  25. M. C. Hollander, G. M. Blumenthal, and P. A. Dennis, “PTEN loss in the continuum of common cancers, rare syndromes and mouse models,” Nature Reviews Cancer, vol. 11, no. 4, pp. 289–301, 2011. View at Publisher · View at Google Scholar · View at PubMed
  26. N. M. Monte, K. A. Webster, D. Neuberg, G. R. Dressler, and G. L. Mutter, “Joint loss of PAX2 and PTEN expression in endometrial precancers and cancer,” Cancer Research, vol. 70, no. 15, pp. 6225–6232, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  27. F. Meng, R. Henson, H. Wehbe-Janek, K. Ghoshal, S. T. Jacob, and T. Patel, “MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer,” Gastroenterology, vol. 133, no. 2, pp. 647–658, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. N. Amodio, M. Scrima, L. Palaia et al., “Oncogenic role of the E3 ubiquitin ligase NEDD4-1, a PTEN negative regulator, in non-small-cell lung carcinomas,” American Journal of Pathology, vol. 177, no. 5, pp. 2622–2634, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. J. C. Soria, H. Y. Lee, J. I. Lee et al., “Lack of PTEN expression in non-small cell lung cancer could be related to promoter methylation,” Clinical Cancer Research, vol. 8, no. 5, pp. 1178–1184, 2002. View at Scopus
  30. C. J. Marsit, S. Zheng, K. Aldape et al., “PTEN expression in non-small-cell lung cancer: evaluating its relation to tumor characteristics, allelic loss, and epigenetic alteration,” Human Pathology, vol. 36, no. 7, pp. 768–776, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  31. Y. E. Whang, X. Wu, H. Suzuki et al., “Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer through loss of expression,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 9, pp. 5246–5250, 1998. View at Publisher · View at Google Scholar · View at Scopus
  32. L. Salmena, A. Carracedo, and P. P. Pandolfi, “Tenets of PTEN tumor suppression,” Cell, vol. 133, no. 3, pp. 403–414, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. 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
  34. A. Suzuki, J. L. De La Pompa, V. Stambolic et al., “High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice,” Current Biology, vol. 8, no. 21, pp. 1169–1178, 1998. View at Scopus
  35. 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 PubMed · View at Scopus
  36. 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 PubMed · View at Scopus
  37. A. Alimonti, A. Carracedo, J. G. Clohessy et al., “Subtle variations in Pten dose determine cancer susceptibility,” Nature Genetics, vol. 42, no. 5, pp. 454–458, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  38. K. Stemke-Hale, A. M. Gonzalez-Angulo, A. Lluch et al., “An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer,” Cancer Research, vol. 68, no. 15, pp. 6084–6091, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  39. B. T. Hennessy, D. L. Smith, P. T. Ram, Y. Lu, and G. B. Mills, “Exploiting the PI3K/AKT pathway for cancer drug discovery,” Nature Reviews Drug Discovery, vol. 4, no. 12, pp. 988–1004, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  40. J. Brugge, M. C. Hung, and G. B. Mills, “A new mutational aktivation in the PI3K pathway,” Cancer Cell, vol. 12, no. 2, pp. 104–107, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  41. 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 PubMed · View at Scopus
  42. F. Vazquez, S. Ramaswamy, N. Nakamura, and W. R. Sellers, “Phosphorylation of the PTEN tail regulates protein stability and function,” Molecular and Cellular Biology, vol. 20, no. 14, pp. 5010–5018, 2000. View at Publisher · View at Google Scholar · View at Scopus
  43. Z. M. Sheng, A. Marchetti, F. Buttitta et al., “Multiple regions of chromosome 6q affected by loss of heterozygosity in primary human breast carcinomas,” British Journal of Cancer, vol. 73, no. 2, pp. 144–147, 1996. View at Scopus
  44. T. Mund and H. R. B. Pelham, “Regulation of PTEN/Akt and MAP kinase signaling pathways by the ubiquitin ligase activators Ndfip1 and Ndfip2,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 25, pp. 11429–11434, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  45. 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 PubMed · View at Scopus
  46. 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 PubMed · View at Scopus
  47. F. Fouladkou, T. Landry, H. Kawabe et al., “The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 25, pp. 8585–8590, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. X. R. Cao, N. L. Lill, N. Boase et al., “Nedd4 controls animal growth by regulating IGF-1 signaling,” Science signaling, vol. 1, no. 38, article ra5, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  49. C. Van Themsche, V. Leblanc, S. Parent, and E. Asselin, “X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization,” Journal of Biological Chemistry, vol. 284, no. 31, pp. 20462–20466, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  50. Q. L. Deveraux, R. Takahashi, G. S. Salvesen, and J. C. Reed, “X-linked IAP is a direct inhibitor of cell-death proteases,” Nature, vol. 388, no. 6639, pp. 300–304, 1997. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  51. A. D. Schimmer, S. Dalili, R. A. Batey, and S. J. Riedl, “Targeting XIAP for the treatment of malignancy,” Cell Death and Differentiation, vol. 13, no. 2, pp. 179–188, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  52. A. Gericke, M. Munson, and A. H. Ross, “Regulation of the PTEN phosphatase,” Gene, vol. 374, no. 1-2, pp. 1–9, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  53. M. Yilmaz and G. Christofori, “Mechanisms of motility in metastasizing cells,” Molecular Cancer Research, vol. 8, no. 5, pp. 629–642, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  54. Y. Zhang, B. Ma, and Q. Fan, “Mechanisms of breast cancer bone metastasis,” Cancer Letters, vol. 292, no. 1, pp. 1–7, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  55. M. Mareel, T. Boterberg, V. Noë et al., “E-cadherin/catenin/cytoskeleton complex: a regulator of cancer invasion,” Journal of Cellular Physiology, vol. 173, no. 2, pp. 271–274, 1997. View at Publisher · View at Google Scholar · View at Scopus
  56. X. Wu, K. Hepner, S. Castelino-Prabhu et al., “Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 8, pp. 4233–4238, 2000. View at Scopus
  57. M. C. Subauste, P. Nalbant, E. D. Adamson, and K. M. Hahn, “Vinculin controls PTEN protein level by maintaining the interaction of the adherens junction protein β-catenin with the scaffolding protein MAGI-2,” Journal of Biological Chemistry, vol. 280, no. 7, pp. 5676–5681, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  58. 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 Scopus
  59. Y. Hu, Z. Li, L. Guo et al., “MAGI-2 Inhibits cell migration and proliferation via PTEN in human hepatocarcinoma cells,” Archives of Biochemistry and Biophysics, vol. 467, no. 1, pp. 1–9, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  60. J. H. Zuo, et al., “Activation of EGFR promotes squamous carcinoma SCC10A cell migration and invasion via inducing EMT-like phenotype change and MMP-9-mediated degradation of E-cadherin,” Journal of Cellular Biochemistry, vol. 112, no. 9, pp. 2508–2517, 2011.
  61. B. Fingleton, C. C. Lynch, T. Vargo-Gogola, and L. M. Matrisian, “Cleavage of E-cadherin by matrix metalloproteinase-7 promotes cellular proliferation in nontransformed cell lines via activation of RhoA,” Journal of Oncology, vol. 2010, Article ID 530745, 11 pages, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  62. L. Mohamet, M. L. Lea, and C. M. Ward, “Abrogation of E-cadherin-mediated cellular aggregation allows proliferation of pluripotent mouse embryonic stem cells in shake flask bioreactors,” PLoS ONE, vol. 5, no. 9, article e12921, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  63. J. C. M. de Freitas Junior, B. D. R. D. Silva, W. F. de Souza, W. M. de Araújo, E. S. F. W. Abdelhay, and J. A. Morgado-Díaz, “Inhibition of N-linked glycosylation by tunicamycin induces E-cadherin-mediated cell-cell adhesion and inhibits cell proliferation in undifferentiated human colon cancer cells,” Cancer Chemotherapy and Pharmacology, vol. 68, no. 1, pp. 227–238, 2011. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  64. S. Rachagani, S. Senapati, S. Chakraborty et al., “Activated Kras G12D is associated with invasion and metastasis of pancreatic cancer cells through inhibition of E-cadherin,” British Journal of Cancer, vol. 104, no. 6, pp. 1038–1048, 2011. View at Publisher · View at Google Scholar · View at PubMed
  65. R. M. Bremnes, R. Veve, F. R. Hirsch, and W. A. Franklin, “The E-cadherin cell-cell adhesion complex and lung cancer invasion, metastasis, and prognosis,” Lung Cancer, vol. 36, no. 2, pp. 115–124, 2002. View at Publisher · View at Google Scholar · View at Scopus
  66. M.-T. Lau, C. Klausen, and P. C. K. Leung, “E-cadherin inhibits tumor cell growth by suppressing PI3K/Akt signaling via beta-catenin-Egr1-mediated PTEN expression,” Oncogene, vol. 30, no. 24, pp. 2753–2766, 2011. View at Publisher · View at Google Scholar · View at PubMed
  67. M. V. Fournier, J. E. Fata, K. J. Martin, P. Yaswen, and M. J. Bissell, “Interaction of E-cadherin and PTEN regulates morphogenesis and growth arrest in human mammary epithelial cells,” Cancer Research, vol. 69, no. 10, pp. 4545–4552, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  68. L. Kotelevets, J. Van Hengel, E. Bruyneel, M. Mareel, F. Van Roy, and E. Chastre, “The lipid phosphatase activity of PTEN is critical for stabilizing intercellular junctions and reverting invasiveness,” Journal of Cell Biology, vol. 155, no. 7, pp. 1129–1135, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  69. N. B. Adey, L. Huang, P. A. Ormonde et al., “Threonine phosphorylation of the MMAC1/PTEN PDZ binding domain both inhibits and stimulates PDZ binding,” Cancer Research, vol. 60, no. 1, pp. 35–37, 2000. View at Scopus
  70. Y. Wu, D. Dowbenko, S. Spencer et al., “Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase,” Journal of Biological Chemistry, vol. 275, no. 28, pp. 21477–21485, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  71. L. Kotelevets, J. Van Hengel, E. Bruyneel, M. Mareel, F. Van Roy, and E. Chastre, “Implication of the MAGI-1b/PTEN signalosome in stabilization of adherens junctions and suppression of invasiveness,” FASEB Journal, vol. 19, no. 1, pp. 115–117, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  72. X. Peng, L. E. Cuff, C. D. Lawton, and K. A. DeMali, “Vinculin regulates cell-surface E-cadherin expression by binding to β-catenin,” Journal of Cell Science, vol. 123, no. 4, pp. 567–577, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  73. T. Virolle, E. D. Adamson, V. Baron et al., “The Egr-1 transcription factor directly activates PTEN during irradiation-induced signalling,” Nature Cell Biology, vol. 3, no. 12, pp. 1124–1128, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  74. T. Sano, H. Lin, X. Chen et al., “Differential expression of MMAC/PTEN in glioblastoma multiforme: relationship to localization and prognosis,” Cancer Research, vol. 59, no. 8, pp. 1820–1824, 1999. View at Scopus
  75. A. Perren, L. P. Weng, A. H. Boag et al., “Immunohistochemical evidence of loss of PTEN expression in primary ductal adenocarcinomas of the breast,” American Journal of Pathology, vol. 155, no. 4, pp. 1253–1260, 1999. View at Scopus
  76. O. Gimm, A. Perren, L. P. Weng et al., “Differential nuclear and cytoplasmic expression of PTEN in normal thyroid tissue, and benign and malignant epithelial thyroid tumors,” American Journal of Pathology, vol. 156, no. 5, pp. 1693–1700, 2000. View at Scopus
  77. S. Semba, S. Satake, M. Matsushita, and H. Yokozaki, “Phosphatase activity of nuclear PTEN is required for CDX2-mediated intestinal differentiation of gastric carcinoma,” Cancer Letters, vol. 274, no. 1, pp. 143–150, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  78. D. C. Whiteman, X. P. Zhou, M. C. Cummings, S. Pavey, N. K. Hayward, and C. Eng, “Nuclear PTEN expression and clinicopathologic features in a population-based series of primary cutaneous melanoma,” International Journal of Cancer, vol. 99, no. 1, pp. 63–67, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  79. K. S. Jang, Y. S. Song, S. H. Jang et al., “Clinicopathological significance of nuclear PTEN expression in colorectal adenocarcinoma,” Histopathology, vol. 56, no. 2, pp. 229–239, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  80. M. E. Ginn-Pease and C. Eng, “Increased nuclear phosphatase and tensin homologue deleted on chromosome 10 is associated with G0-G1 in MCF-7 cells,” Cancer Research, vol. 63, no. 2, pp. 282–286, 2003. View at Scopus
  81. J. H. Chung and C. Eng, “Nuclear-cytoplasmic partitioning of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) differentially regulates the cell cycle and apoptosis,” Cancer Research, vol. 65, no. 18, pp. 8096–8100, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  82. A. I. Jacob, T. Romigh, K. A. Waite, and C. Eng, “Nuclear PTEN levels and G2 progression in melanoma cells,” Melanoma research, vol. 19, no. 4, pp. 203–210, 2009. View at Scopus
  83. M. Tachibana, M. Shibakita, S. Ohno et al., “Expression and prognostic significance of PTEN product protein in patients with esophageal squamous cell carcinoma,” Cancer, vol. 94, no. 7, pp. 1955–1960, 2002. View at Publisher · View at Google Scholar · View at Scopus
  84. X. P. Zhou, A. Loukola, R. Salovaara et al., “PTEN mutational spectra, expression levels, and subcellular localization in microsatellite stable and unstable colorectal cancers,” American Journal of Pathology, vol. 161, no. 2, pp. 439–447, 2002. View at Scopus
  85. S. M. Planchon, K. A. Waite, and C. Eng, “The nuclear affairs of PTEN,” Journal of Cell Science, vol. 121, no. 3, pp. 249–253, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  86. F. Liu, S. Wagner, R. B. Campbell, J. A. Nickerson, C. A. Schiffer, and A. H. Ross, “PTEN enters the nucleus by diffusion,” Journal of Cellular Biochemistry, vol. 96, no. 2, pp. 221–234, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  87. T. Boulikas, “Nuclear localization signals (NLS),” Critical Reviews in Eukaryotic Gene Expression, vol. 3, no. 3, pp. 193–227, 1993. View at Scopus
  88. R. Peters, “Fluorescence microphotolysis to measure nucleocytoplasmic transport and intracellular mobility,” Biochimica et Biophysica Acta, vol. 864, no. 3-4, pp. 305–359, 1986. View at Scopus
  89. S. Kuersten, M. Ohno, and I. W. Mattaj, “Nucleocytoplasmic transport: ran, beta and beyond,” Trends in Cell Biology, vol. 11, no. 12, pp. 497–503, 2001. View at Publisher · View at Google Scholar · View at Scopus
  90. A. Gil, A. Andrés-Pons, E. Fernândez et al., “Nuclear localization of PTEN by a Ran-dependent mechanism enhances apoptosis: involvement of an N-terminal nuclear localization domain and multiple nuclear exclusion motifs,” Molecular Biology of the Cell, vol. 17, no. 9, pp. 4002–4013, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  91. M. H. Mossink, A. Van Zon, R. J. Scheper, P. Sonneveld, and E. A. C. Wiemer, “Vaults: a ribonucleoprotein particle involved in drug resistance?” Oncogene, vol. 22, no. 47, pp. 7458–7467, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  92. Y. Zhenbao, N. Fotouhi-Ardakani, L. Wu et al., “PTEN associates with the vault particles in HeLa cells,” Journal of Biological Chemistry, vol. 277, no. 43, pp. 40247–40252, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  93. J. Torres and R. Pulido, “The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus. Implications for PTEN stability to proteasome-mediated degradation,” Journal of Biological Chemistry, vol. 276, no. 2, pp. 993–998, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  94. M. M. Georgescu, K. H. Kirsch, T. Akagi, T. Shishido, and H. Hanafusa, “The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 18, pp. 10182–10187, 1999. View at Scopus
  95. J. Torres, J. Rodriguez, M. P. Myers et al., “Phosphorylation-regulated cleavage of the tumor suppressor PTEN by caspase-3. Implications for the control of protein stability and PTEN-protein interactions,” Journal of Biological Chemistry, vol. 278, no. 33, pp. 30652–30660, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  96. M. Raftopoulou, S. Etienne-Manneville, A. Self, S. Nicholls, and A. Hall, “Regulation of cell migration by the C2 domain of the tumor suppressor PTEN,” Science, vol. 303, no. 5661, pp. 1179–1181, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  97. L. Odriozola, G. Singh, T. Hoang, and A. M. Chan, “Regulation of PTEN activity by its carboxyl-terminal autoinhibitory domain,” Journal of Biological Chemistry, vol. 282, no. 32, pp. 23306–23315, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  98. C. J. Chang, D. J. Mulholland, B. Valamehr, S. Mosessian, W. R. Sellers, and H. Wu, “PTEN nuclear localization is regulated by oxidative stress and mediates p53-dependent tumor suppression,” Molecular and Cellular Biology, vol. 28, no. 10, pp. 3281–3289, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  99. J. L. Liu, Z. Mao, T. A. LaFortune et al., “Cell cycle-dependent nuclear export of phosphatase and tensin homologue tumor suppressor is regulated by the phosphoinositide-3-kinase signaling cascade,” Cancer Research, vol. 67, no. 22, pp. 11054–11063, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  100. J.-L. Liu, Z. Mao, G. E. Gallick, and W. K.A. Yung, “AMPK/TSC2/mTOR-signaling intermediates are not necessary for LKB1-mediated nuclear retention of PTEN tumor suppressor,” Neuro-Oncology, vol. 13, no. 2, pp. 184–194, 2011. View at Publisher · View at Google Scholar · View at PubMed
  101. M. S. Song, A. Carracedo, L. Salmena et al., “Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner,” Cell, vol. 144, no. 2, pp. 187–199, 2011. View at Publisher · View at Google Scholar · View at PubMed
  102. T. Cardozo and M. Pagano, “The SCF ubiquitin ligase: insights into a molecular machine,” Nature Reviews Molecular Cell Biology, vol. 5, no. 9, pp. 739–751, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  103. J. M. Peters, “The anaphase promoting complex/cyclosome: a machine designed to destroy,” Nature Reviews Molecular Cell Biology, vol. 7, no. 9, pp. 644–656, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  104. J. Pines, “Mitosis: a matter of getting rid of the right protein at the right time,” Trends in Cell Biology, vol. 16, no. 1, pp. 55–63, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  105. M. Sullivan and D. O. Morgan, “Finishing mitosis, one step at a time,” Nature Reviews Molecular Cell Biology, vol. 8, no. 11, pp. 894–903, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  106. S. M. Hammond, “RNAi, microRNAs, and human disease,” Cancer Chemotherapy and Pharmacology, vol. 58, pp. s63–s68, 2006. View at Publisher · View at Google Scholar · View at PubMed
  107. V. Ambros, “MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing,” Cell, vol. 113, no. 6, pp. 673–676, 2003. View at Publisher · View at Google Scholar · View at Scopus
  108. S. Bagga, “Posttransplant lymphoproliferative disease in a pediatric patient as seen on PET/CT scan,” Clinical Nuclear Medicine, vol. 32, no. 7, pp. 553–554, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  109. D. P. Bartel, “MicroRNAs: genomics, biogenesis, mechanism, and function,” Cell, vol. 116, no. 2, pp. 281–297, 2004. View at Publisher · View at Google Scholar · View at Scopus
  110. K. K. H. Farh, A. Grimson, C. Jan et al., “The widespread impact of mammalian microRNAs on mRNA repression and evolution,” Science, vol. 310, no. 5755, pp. 1817–1821, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  111. D. S. Schwarz, G. Hutvágner, T. Du, Z. Xu, N. Aronin, and P. D. Zamore, “Asymmetry in the assembly of the RNAi enzyme complex,” Cell, vol. 115, no. 2, pp. 199–208, 2003. View at Publisher · View at Google Scholar · View at Scopus
  112. T. Li, D. Li, J. Sha, P. Sun, and Y. Huang, “MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells,” Biochemical and Biophysical Research Communications, vol. 383, no. 3, pp. 280–285, 2009. View at Publisher · View at Google Scholar · View at PubMed
  113. Z. Liang, H. Wu, S. Reddy et al., “Blockade of invasion and metastasis of breast cancer cells via targeting CXCR4 with an artificial microRNA,” Biochemical and Biophysical Research Communications, vol. 363, no. 3, pp. 542–546, 2007. View at Publisher · View at Google Scholar · View at PubMed
  114. L. X. Yan, X. F. Huang, Q. Shao et al., “MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis,” RNA, vol. 14, no. 11, pp. 2348–2360, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  115. S. F. Tavazoie, C. Alarcón, T. Oskarsson et al., “Endogenous human microRNAs that suppress breast cancer metastasis,” Nature, vol. 451, no. 7175, pp. 147–152, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  116. S. Valastyan, F. Reinhardt, N. Benaich et al., “A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis,” Cell, vol. 137, no. 6, pp. 1032–1046, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  117. X. F. Li, P. J. Yan, and Z. M. Shao, “Downregulation of miR-193b contributes to enhance urokinase-type plasminogen activator (uPA) expression and tumor progression and invasion in human breast cancer,” Oncogene, vol. 28, no. 44, pp. 3937–3948, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  118. J. G. Zhang, J. J. Wang, F. Zhao, Q. Liu, K. Jiang, and G. H. Yang, “MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC),” Clinica Chimica Acta, vol. 411, no. 11-12, pp. 846–852, 2011. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  119. X. Ma, M. Kumar, S. N. Choudhury et al., “Loss of the miR-21 allele elevates the expression of its target genes and reduces tumorigenesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 25, pp. 10144–10149, 2011. View at Publisher · View at Google Scholar · View at PubMed
  120. L. Qi, J. Bart, L. P. Tan et al., “Expression of miR-21 and its targets (PTEN, PDCD4, TM1) in flat epithelial atypia of the breast in relation to ductal carcinoma in situ and invasive carcinoma,” BMC Cancer, vol. 9, article 163, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  121. M. Folini, P. Gandellini, N. Longoni et al., “miR-21: an oncomir on strike in prostate cancer,” Molecular Cancer, vol. 9, article 12, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  122. H. Yang, W. Kong, L. He et al., “MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN,” Cancer Research, vol. 68, no. 2, pp. 425–433, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  123. A. M. Cheng, M. W. Byrom, J. Shelton, and L. P. Ford, “Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis,” Nucleic Acids Research, vol. 33, no. 4, pp. 1290–1297, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  124. X. Xiong, H.-Z. Ren, M.-H. Li, J.-H. Mei, J.-F. Wen, and C.-L. Zheng, “Down-regulated miRNA-214 induces a cell cycle G1 arrest in gastric cancer cells by up-regulating the PTEN protein,” Pathology and Oncology Research, vol. 17, no. 4, pp. 931–937, 2011. View at Publisher · View at Google Scholar · View at PubMed
  125. C. Wang, Z. Bian, D. Wei, and J.-G. Zhang, “miR-29b regulates migration of human breast cancer cells,” Molecular and Cellular Biochemistry, vol. 352, no. 1-2, pp. 197–207, 2011. View at Publisher · View at Google Scholar · View at PubMed
  126. C. Zhang, C. Kang, P. Wang et al., “MICRORNA-221 and -222 regulate radiation sensitivity by targeting the PTEN pathway,” International Journal of Radiation Oncology Biology Physics, vol. 80, no. 1, pp. 240–248, 2011. View at Publisher · View at Google Scholar · View at PubMed