Focus on PTEN regulation

Frontiers in Oncology

Volumn 5, Issue JUL, 2015, Pages

  Brito, Miriam Bermúdez ^a   Goulielmaki, Evangelia ^a   Papakonstanti, Evangelia A ^a  

^a UNIVERSITY OF CRETE   (Greece)

Author keywords

Localization; Protein interactions; PTEN; Transcription; Translation

Indexed keywords

MICRORNA; PHOSPHATIDATE PHOSPHATASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE;

CELL FUNCTION; CELL METABOLISM; ENZYME ACTIVITY; EPIGENETICS; HUMAN; NEOPLASM; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN STRUCTURE; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION; TRANSLATION REGULATION; UBIQUITINATION;

EID: 84940102809     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2015.00166     Document Type: Review

References (214)

1. Govender D, Chetty R. Gene of the month: PTEN. J Clin Pathol (2012) 65:601-3. doi:10.1136/jclinpath-2012-200711.
2. Li DM, Sun H. TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta. Cancer Res (1997) 57:2124-9.
3. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science (1997) 275:1943-7. doi:10.1126/science.275.5308.1943.
4. Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, et al. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet (1997) 15:356-62. doi:10.1038/ng0497-356.
5. Di Cristofano A, Pandolfi PP. The multiple roles of PTEN in tumor suppression. Cell (2000) 100:387-90. doi:10.1016/S0092-8674(00)80674-1.
6. Xu WT, Yang Z, Lu NH. Roles of PTEN (phosphatase and tensin homolog) in gastric cancer development and progression. Asian Pac J Cancer Prev (2014) 15:17-24. doi:10.7314/APJCP.2014.15.1.17.
7. Myers MP, Tonks NK. PTEN: sometimes taking it off can be better than putting it on. Am J Hum Genet (1997) 61:1234-8. doi:10.1086/301659.
8. Ye B, Jiang LL, Xu HT, Zhou DW, Li ZS. Expression of PI3K/AKT pathway in gastric cancer and its blockade suppresses tumor growth and metastasis. Int J Immunopathol Pharmacol (2012) 25:627-36.
9. Vanhaesebroeck B, Leevers SJ, Panayotou G, Waterfield MD. Phosphoinositide 3-kinases: a conserved family of signal transducers. Trends Biochem Sci (1997) 22:267-72. doi:10.1016/S0968-0004(97)01061-X.
10. Vanhaesebroeck B, Guillermet-Guibert J, Graupera M, Bilanges B. The emerging mechanisms of isoform-specific PI3K signalling. Nat Rev Mol Cell Biol (2010) 11:329-41. doi:10.1038/nrm2882.
11. Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet (2006) 7:606-19. doi:10.1038/nrg1879.
12. Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov (2009) 8:627-44. doi:10.1038/nrd2926.
13. Stephens LR, Eguinoa A, Erdjument-Bromage H, Lui M, Cooke F, Coadwell J, et al. The G beta gamma sensitivity of a PI3K is dependent upon a tightly associated adaptor, p101. Cell (1997) 89:105-14. doi:10.1016/S0092-8674(00)80187-7.
14. Krugmann S, Hawkins PT, Pryer N, Braselmann S. Characterizing the interactions between the two subunits of the p101/p110gamma phosphoinositide 3-kinase and their role in the activation of this enzyme by G beta gamma subunits. J Biol Chem (1999) 274:17152-8. doi:10.1074/jbc.274.24.17152.
15. Suire S, Coadwell J, Ferguson GJ, Davidson K, Hawkins P, Stephens L. p84, a new gbetagamma-activated regulatory subunit of the type IB phosphoinositide 3-kinase p110gamma. Curr Biol (2005) 15:566-70. doi:10.1016/j.cub.2005.02.020.
16. Voigt P, Dorner MB, Schaefer M. Characterization of p87PIKAP, a novel regulatory subunit of phosphoinositide 3-kinase gamma that is highly expressed in heart and interacts with PDE3B. J Biol Chem (2006) 281:9977-86. doi:10.1074/jbc.M512502200.
17. Davies MA. Regulation, role, and targeting of Akt in cancer. J Clin Oncol (2011) 29:4715-7. doi:10.1200/JCO.2011.37.4751.
18. Vanhaesebroeck B, Leevers SJ, Ahmadi K, Timms J, Katso R, Driscoll PC, et al. Synthesis and function of 3-phosphorylated inositol lipids. Annu Rev Biochem (2001) 70:535-602. doi:10.1146/annurev.biochem.70.1.535.
19. Alessi DR, Deak M, Casamayor A, Caudwell FB, Morrice N, Norman DG, et al. 3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase. Curr Biol (1997) 7:776-89. doi:10.1016/S0960-9822(06)00336-8.
20. Maehama T, Dixon JE. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem (1998) 273:13375-8. doi:10.1074/jbc.273.22.13375.
21. Leevers SJ, Vanhaesebroeck B, Waterfield MD. Signalling through phosphoinositide 3-kinases: the lipids take centre stage. Curr Opin Cell Biol (1999) 11:219-25. doi:10.1016/S0955-0674(99)80029-5.
22. Leslie NR, Downes CP. PTEN function: how normal cells control it and tumour cells lose it. Biochem J (2004) 382:1-11. doi:10.1042/BJ20040825.
23. Parsons R. Human cancer, PTEN and the PI-3 kinase pathway. Semin Cell Dev Biol (2004) 15:171-6. doi:10.1016/j.semcdb.2003.12.021.
24. Sansal I, Sellers WR. The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol (2004) 22:2954-63. doi:10.1200/JCO.2004.02.141.
25. Cully M, You H, Levine AJ, Mak TW. Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer (2006) 6:184-92. doi:10.1038/nrc1819.
26. Li DM, Sun H. PTEN/MMAC1/TEP1 suppresses the tumorigenicity and induces G1 cell cycle arrest in human glioblastoma cells. Proc Natl Acad Sci U S A (1998) 95:15406-11. doi:10.1073/pnas.95.26.15406.
27. Norimatsu Y, Moriya T, Kobayashi TK, Sakurai T, Shimizu K, Tsukayama C, et al. Immunohistochemical expression of PTEN and beta-catenin for endometrial intraepithelial neoplasia in Japanese women. Ann Diagn Pathol (2007) 11:103-8. doi:10.1016/j.anndiagpath.2006.06.009.
28. Mackay HJ, Gallinger S, Tsao MS, Mclachlin CM, Tu D, Keiser K, et al. Prognostic value of microsatellite instability (MSI) and PTEN expression in women with endometrial cancer: results from studies of the NCIC clinical trials group (NCIC CTG). Eur J Cancer (2010) 46:1365-73. doi:10.1016/j.ejca.2010.02.031.
29. You Y, Geng X, Zhao P, Fu Z, Wang C, Chao S, et al. Evaluation of combination gene therapy with PTEN and antisense hTERT for malignant glioma in vitro and xenografts. Cell Mol Life Sci (2007) 64:621-31. doi:10.1007/s00018-007-6424-4.
30. Xu J, Li Z, Wang J, Chen H, Fang JY. Combined PTEN mutation and protein expression associate with overall and disease-free survival of glioblastoma patients. Transl Oncol (2014) 7(196-205):e191. doi:10.1016/j.tranon.2014.02.004.
31. Romano C, Schepis C. PTEN gene: a model for genetic diseases in dermatology. ScientificWorldJournal (2012) 2012:252457. doi:10.1100/2012/252457.
32. Baig RM, Mahjabeen I, Sabir M, Masood N, Hafeez S, Malik FA, et al. Genetic changes in the PTEN gene and their association with breast cancer in Pakistan. Asian Pac J Cancer Prev (2011) 12:2773-8.
33. Davis NM, Sokolosky M, Stadelman K, Abrams SL, Libra M, Candido S, et al. Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention. Oncotarget (2014) 5:4603-50.
34. Patel R, Gao M, Ahmad I, Fleming J, Singh LB, Rai TS, et al. Sprouty2, PTEN, and PP2A interact to regulate prostate cancer progression. J Clin Invest (2013) 123:1157-75. doi:10.1172/JCI63672.
35. Birnbaum Y, Nanhwan MK, Ling S, Perez-Polo JR, Ye Y, Bajaj M. PTEN upregulation may explain the development of insulin resistance and type 2 diabetes with high dose statins. Cardiovasc Drugs Ther (2014) 28:447-57. doi:10.1007/s10557-014-6546-5.
36. Worby CA, Dixon JE. Pten. Annu Rev Biochem (2014) 83:641-69. doi:10.1146/annurev-biochem-082411-113907.
37. Shi Y, Paluch BE, Wang X, Jiang X. PTEN at a glance. J Cell Sci (2012) 125:4687-92. doi:10.1242/jcs.093765.
38. Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol (2012) 13:283-96. doi:10.1038/nrm3330.
39. Patel L, Pass I, Coxon P, Downes CP, Smith SA, Macphee CH. Tumor suppressor and anti-inflammatory actions of PPARgamma agonists are mediated via upregulation of PTEN. Curr Biol (2001) 11:764-8. doi:10.1016/S0960-9822(01)00225-1.
40. Stambolic V, Macpherson D, Sas D, Lin Y, Snow B, Jang Y, et al. Regulation of PTEN transcription by p53. Mol Cell (2001) 8:317-25. doi:10.1016/S1097-2765(01)00323-9.
41. Virolle T, Adamson ED, Baron V, Birle D, Mercola D, Mustelin T, et al. The Egr-1 transcription factor directly activates PTEN during irradiation-induced signalling. Nat Cell Biol (2001) 3:1124-8. doi:10.1038/ncb1201-1124.
42. Edwin F, Singh R, Endersby R, Baker SJ, Patel TB. The tumor suppressor PTEN is necessary for human sprouty 2-mediated inhibition of cell proliferation. J Biol Chem (2006) 281:4816-22. doi:10.1074/jbc.M508300200.
43. Hettinger K, Vikhanskaya F, Poh MK, Lee MK, De Belle I, Zhang JT, et al. c-Jun promotes cellular survival by suppression of PTEN. Cell Death Differ (2007) 14:218-29. doi:10.1038/sj.cdd.4401946.
44. Vasudevan KM, Gurumurthy S, Rangnekar VM. Suppression of PTEN expression by NF-kappa B prevents apoptosis. Mol Cell Biol (2004) 24:1007-21. doi:10.1128/MCB.24.3.1007-1021.2004.
45. Gericke A, Munson M, Ross AH. Regulation of the PTEN phosphatase. Gene (2006) 374:1-9. doi:10.1016/j.gene.2006.02.024.
46. Song LB, Li J, Liao WT, Feng Y, Yu CP, Hu LJ, et al. The polycomb group protein Bmi-1 represses the tumor suppressor PTEN and induces epithelial-mesenchymal transition in human nasopharyngeal epithelial cells. J Clin Invest (2009) 119:3626-36. doi:10.1172/JCI39374.
47. Lau MT, Klausen C, Leung PC. E-cadherin inhibits tumor cell growth by suppressing PI3K/Akt signaling via beta-catenin-Egr1-mediated PTEN expression. Oncogene (2011) 30:2753-66. doi:10.1038/onc.2011.6.
48. Meng X, Wang Y, Zheng X, Liu C, Su B, Nie H, et al. shRNA-mediated knockdown of Bmi-1 inhibit lung adenocarcinoma cell migration and metastasis. Lung Cancer (2012) 77:24-30. doi:10.1016/j.lungcan.2012.02.015.
49. Kang YH, Lee HS, Kim WH. Promoter methylation and silencing of PTEN in gastric carcinoma. Lab Invest (2002) 82:285-91. doi:10.1038/labinvest.3780422.
50. Garcia JM, Silva J, Pena C, Garcia V, Rodriguez R, Cruz MA, et al. Promoter methylation of the PTEN gene is a common molecular change in breast cancer. Genes Chromosomes Cancer (2004) 41:117-24. doi:10.1002/gcc.20062.
51. Goel A, Arnold CN, Niedzwiecki D, Carethers JM, Dowell JM, Wasserman L, et al. Frequent inactivation of PTEN by promoter hypermethylation in microsatellite instability-high sporadic colorectal cancers. Cancer Res (2004) 64:3014-21. doi:10.1158/0008-5472.CAN-2401-2.
52. Mirmohammadsadegh A, Marini A, Nambiar S, Hassan M, Tannapfel A, Ruzicka T, et al. Epigenetic silencing of the PTEN gene in melanoma. Cancer Res (2006) 66:6546-52. doi:10.1158/0008-5472.CAN-06-0384.
53. Zysman MA, Chapman WB, Bapat B. Considerations when analyzing the methylation status of PTEN tumor suppressor gene. Am J Pathol (2002) 160:795-800. doi:10.1016/S0002-9440(10)64902-4.
54. Hesson LB, Packham D, Pontzer E, Funchain P, Eng C, Ward RL. A reinvestigation of somatic hypermethylation at the PTEN CpG island in cancer cell lines. Biol Proced Online (2012) 14:5. doi:10.1186/1480-9222-14-5.
55. Hesson LB, Ward RL. Discrimination of pseudogene and parental gene DNA methylation using allelic bisulfite sequencing. Methods Mol Biol (2014) 1167:265-74. doi:10.1007/978-1-4939-0835-6_18.
56. Palomero T, Sulis ML, Cortina M, Real PJ, Barnes K, Ciofani M, et al. Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Nat Med (2007) 13:1203-10. doi:10.1038/nm1636.
57. Chappell WH, Green TD, Spengeman JD, Mccubrey JA, Akula SM, Bertrand FE. Increased protein expression of the PTEN tumor suppressor in the presence of constitutively active Notch-1. Cell Cycle (2005) 4:1389-95. doi:10.4161/cc.4.10.2028.
58. Whelan JT, Forbes SL, Bertrand FE. CBF-1 (RBP-J kappa) binds to the PTEN promoter and regulates PTEN gene expression. Cell Cycle (2007) 6:80-4. doi:10.4161/cc.6.1.3648.
59. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell (2004) 116:281-97. doi:10.1016/S0092-8674(04)00045-5.
60. Bartel DP, Chen CZ. Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs. Nat Rev Genet (2004) 5:396-400. doi:10.1038/nrg1328.
61. van den Berg A, Mols J, Han J. RISC-target interaction: cleavage and translational suppression. Biochim Biophys Acta (2008) 1779:668-77. doi:10.1016/j.bbagrm.2008.07.005.
62. Ambros V. The functions of animal microRNAs. Nature (2004) 431:350-5. doi:10.1038/nature02871.
63. Miska EA. How microRNAs control cell division, differentiation and death. Curr Opin Genet Dev (2005) 15:563-8. doi:10.1016/j.gde.2005.08.005.
64. Wilmott JS, Zhang XD, Hersey P, Scolyer RA. The emerging important role of microRNAs in the pathogenesis, diagnosis and treatment of human cancers. Pathology (2011) 43:657-71. doi:10.1097/PAT.0b013e32834a7358.
65. Nair VS, Maeda LS, Ioannidis JP. Clinical outcome prediction by microRNAs in human cancer: a systematic review. J Natl Cancer Inst (2012) 104:528-40. doi:10.1093/jnci/djs027.
66. Hunt S, Jones AV, Hinsley EE, Whawell SA, Lambert DW. MicroRNA-124 suppresses oral squamous cell carcinoma motility by targeting ITGB1. FEBS Lett (2011) 585:187-92. doi:10.1016/j.febslet.2010.11.038.
67. Wu L, Cai C, Wang X, Liu M, Li X, Tang H. MicroRNA-142-3p, a new regulator of RAC1, suppresses the migration and invasion of hepatocellular carcinoma cells. FEBS Lett (2011) 585:1322-30. doi:10.1016/j.febslet.2011.03.067.
68. Wang Z, Zhang X, Yang Z, Du H, Wu Z, Gong J, et al. MiR-145 regulates PAK4 via the MAPK pathway and exhibits an antitumor effect in human colon cells. Biochem Biophys Res Commun (2012) 427:444-9. doi:10.1016/j.bbrc.2012.06.123.
69. Lin SC, Liu CJ, Lin JA, Chiang WF, Hung PS, Chang KW. miR-24 up-regulation in oral carcinoma: positive association from clinical and in vitro analysis. Oral Oncol (2010) 46:204-8. doi:10.1016/j.oraloncology.2009.12.005.
70. Liu C, Yu J, Yu S, Lavker RM, Cai L, Liu W, et al. MicroRNA-21 acts as an oncomir through multiple targets in human hepatocellular carcinoma. J Hepatol (2010) 53:98-107. doi:10.1016/j.jhep.2010.02.021.
71. Yang L, Li Q, Wang Q, Jiang Z, Zhang L. Silencing of miRNA-218 promotes migration and invasion of breast cancer via Slit2-Robo1 pathway. Biomed Pharmacother (2012) 66:535-40. doi:10.1016/j.biopha.2012.04.006.
72. He L. Posttranscriptional regulation of PTEN dosage by noncoding RNAs. Sci Signal (2010) 3:e39. doi:10.1126/scisignal.3146pe39.
73. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology (2007) 133:647-58. doi:10.1053/j.gastro.2007.05.022.
74. Wang B, Majumder S, Nuovo G, Kutay H, Volinia S, Patel T, et al. Role of microRNA-155 at early stages of hepatocarcinogenesis induced by choline-deficient and amino acid-defined diet in C57BL/6 mice. Hepatology (2009) 50:1152-61. doi:10.1002/hep.23100.
75. Poliseno L, Salmena L, Riccardi L, Fornari A, Song MS, Hobbs RM, 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. Sci Signal (2010) 3:ra29. doi:10.1126/scisignal.2000594.
76. Jindra PT, Bagley J, Godwin JG, Iacomini J. Costimulation-dependent expression of microRNA-214 increases the ability of T cells to proliferate by targeting Pten. J Immunol (2010) 185:990-7. doi:10.4049/jimmunol.1000793.
77. Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B, Wang J, et al. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol (2008) 9:405-14. doi:10.1038/ni1575.
78. Mu P, Han YC, Betel D, Yao E, Squatrito M, Ogrodowski P, et al. Genetic dissection of the miR-17~92 cluster of microRNAs in Myc-induced B-cell lymphomas. Genes Dev (2009) 23:2806-11. doi:10.1101/gad.1872909.
79. Olive V, Bennett MJ, Walker JC, Ma C, Jiang I, Cordon-Cardo C, et al. miR-19 is a key oncogenic component of mir-17-92. Genes Dev (2009) 23:2839-49. doi:10.1101/gad.1861409.
80. Liu ZL, Wang H, Liu J, Wang ZX. MicroRNA-21 (miR-21) expression promotes growth, metastasis, and chemo-or radioresistance in non-small cell lung cancer cells by targeting PTEN. Mol Cell Biochem (2013) 372:35-45. doi:10.1007/s11010-012-1443-3.
81. Xiong Y, Zhang YY, Wu YY, Wang XD, Wan LH, Li L, et al. Correlation of over-expressions of miR-21 and Notch-1 in human colorectal cancer with clinical stages. Life Sci (2014) 106:19-24. doi:10.1016/j.lfs.2014.04.017.
82. Lou Y, Yang X, Wang F, Cui Z, Huang Y. MicroRNA-21 promotes the cell proliferation, invasion and migration abilities in ovarian epithelial carcinomas through inhibiting the expression of PTEN protein. Int J Mol Med (2010) 26:819-27. doi:10.3892/ijmm_00000530.
83. Dong G, Liang X, Wang D, Gao H, Wang L, Wang L, et al. High expression of miR-21 in triple-negative breast cancers was correlated with a poor prognosis and promoted tumor cell in vitro proliferation. Med Oncol (2014) 31:57. doi:10.1007/s12032-014-0057-x.
84. Iliopoulos D, Jaeger SA, Hirsch HA, Bulyk ML, Struhl K. STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol Cell (2010) 39:493-506. doi:10.1016/j.molcel.2010.07.023.
85. Yang H, Kong W, He L, Zhao JJ, O'Donnell JD, Wang J, et al. MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res (2008) 68:425-33. doi:10.1158/0008-5472.CAN-07-2488.
86. Penna E, Orso F, Taverna D. miR-214 as a key hub that controls cancer networks: small player, multiple functions. J Invest Dermatol (2015) 135:960-9. doi:10.1038/jid.2014.479.
87. Fu X, Tian J, Zhang L, Chen Y, Hao Q. Involvement of microRNA-93, a new regulator of PTEN/Akt signaling pathway, in regulation of chemotherapeutic drug cisplatin chemosensitivity in ovarian cancer cells. FEBS Lett (2012) 586:1279-86. doi:10.1016/j.febslet.2012.03.006.
88. Yang L, Li N, Wang H, Jia X, Wang X, Luo J. Altered microRNA expression in cisplatin-resistant ovarian cancer cells and upregulation of miR-130a associated with MDR1/P-glycoprotein-mediated drug resistance. Oncol Rep (2012) 28:592-600. doi:10.3892/or.2012.1823.
89. Li NW, Wang HJ, Yang LY, Jia XB, Chen C, Wang X. [Regulatory effects and associated mechanisms of miR-130a molecules on cisplatin resistance in ovarian cancer A2780 cell lines]. Sichuan Da Xue Xue Bao Yi Xue Ban (2013) 44:865-70.
90. Xie Q, Yan Y, Huang Z, Zhong X, Huang L. MicroRNA-221 targeting PI3-K/Akt signaling axis induces cell proliferation and BCNU resistance in human glioblastoma. Neuropathology (2014) 34:455-64. doi:10.1111/neup.12129.
91. Huse JT, Brennan C, Hambardzumyan D, Wee B, Pena J, Rouhanifard SH, et al. The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo. Genes Dev (2009) 23:1327-37. doi:10.1101/gad.1777409.
92. Liu B, Wu X, Liu B, Wang C, Liu Y, Zhou Q, et al. MiR-26a enhances metastasis potential of lung cancer cells via AKT pathway by targeting PTEN. Biochim Biophys Acta (2012) 1822:1692-704. doi:10.1016/j.bbadis.2012.07.019.
93. Lang Y, Xu S, Ma J, Wu J, Jin S, Cao S, et al. MicroRNA-429 induces tumorigenesis of human non-small cell lung cancer cells and targets multiple tumor suppressor genes. Biochem Biophys Res Commun (2014) 450:154-9. doi:10.1016/j.bbrc.2014.05.084.
94. Wang C, Bian Z, Wei D, Zhang JG. miR-29b regulates migration of human breast cancer cells. Mol Cell Biochem (2011) 352:197-207. doi:10.1007/s11010-011-0755-z.
95. Shi W, Gerster K, Alajez NM, Tsang J, Waldron L, Pintilie M, et al. MicroRNA-301 mediates proliferation and invasion in human breast cancer. Cancer Res (2011) 71:2926-37. doi:10.1158/0008-5472.CAN-10-3369.
96. Ma F, Zhang J, Zhong L, Wang L, Liu Y, Wang Y, et al. Upregulated microRNA-301a in breast cancer promotes tumor metastasis by targeting PTEN and activating Wnt/beta-catenin signaling. Gene (2014) 535:191-7. doi:10.1016/j.gene.2013.11.035.
97. Wu Z, He B, He J, Mao X. Upregulation of miR-153 promotes cell proliferation via downregulation of the PTEN tumor suppressor gene in human prostate cancer. Prostate (2013) 73:596-604. doi:10.1002/pros.22600.
98. Tian L, Fang YX, Xue JL, Chen JZ. Four microRNAs promote prostate cell proliferation with regulation of PTEN and its downstream signals in vitro. PLoS One (2013) 8:e75885. doi:10.1371/journal.pone.0075885.
99. Ke TW, Wei PL, Yeh KT, Chen WT, Cheng YW. MiR-92a promotes cell metastasis of colorectal cancer through PTEN-mediated PI3K/AKT pathway. Ann Surg Oncol (2014). doi:10.1245/s10434-014-4305-2.
100. Sun HB, Chen X, Ji H, Wu T, Lu HW, Zhang Y, et al. miR494 is an independent prognostic factor and promotes cell migration and invasion in colorectal cancer by directly targeting PTEN. Int J Oncol (2014) 45:2486-94. doi:10.3892/ijo.2014.2665.
101. Geng L, Sun B, Gao B, Wang Z, Quan C, Wei F, et al. MicroRNA-103 promotes colorectal cancer by targeting tumor suppressor DICER and PTEN. Int J Mol Sci (2014) 15:8458-72. doi:10.3390/ijms15058458.
102. Wu W, Yang J, Feng X, Wang H, Ye S, Yang P, et al. MicroRNA-32 (miR-32) regulates phosphatase and tensin homologue (PTEN) expression and promotes growth, migration, and invasion in colorectal carcinoma cells. Mol Cancer (2013) 12:30. doi:10.1186/1476-4598-12-30.
103. Yan SY, Chen MM, Li GM, Wang YQ, Fan JG. MiR-32 induces cell proliferation, migration, and invasion in hepatocellular carcinoma by targeting PTEN. Tumour Biol (2015). doi:10.1007/s13277-015-3124-9.
104. Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet (2009) 10:704-14. doi:10.1038/nrg2634.
105. Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell (2011) 146:353-8. doi:10.1016/j.cell.2011.07.014.
106. Cheng DL, Xiang YY, Ji LJ, Lu XJ. Competing endogenous RNA interplay in cancer: mechanism, methodology, and perspectives. Tumour Biol (2015) 36:479-88. doi:10.1007/s13277-015-3093-z.
107. Kartha RV, Subramanian S. Competing endogenous RNAs (ceRNAs): new entrants to the intricacies of gene regulation. Front Genet (2014) 5:8. doi:10.3389/fgene.2014.00008.
108. de Giorgio A, Krell J, Harding V, Stebbing J, Castellano L. Emerging roles of competing endogenous RNAs in cancer: insights from the regulation of PTEN. Mol Cell Biol (2013) 33:3976-82. doi:10.1128/MCB.00683-13.
109. Ergun S, Oztuzcu S. Oncocers: ceRNA-mediated cross-talk by sponging miRNAs in oncogenic pathways. Tumour Biol (2015) 36(5):3129-36. doi:10.1007/s13277-015-3346-x.
110. Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature (2010) 465:1033-8. doi:10.1038/nature09144.
111. Johnsson P, Ackley A, Vidarsdottir L, Lui WO, Corcoran M, Grander D, et al. A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells. Nat Struct Mol Biol (2013) 20:440-6. doi:10.1038/nsmb.2516.
112. Tay Y, Kats L, Salmena L, Weiss D, Tan SM, Ala U, et al. Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell (2011) 147:344-57. doi:10.1016/j.cell.2011.09.029.
113. Guil S, Esteller M. RNA-RNA interactions in gene regulation: the coding and noncoding players. Trends Biochem Sci (2015) 40:248-56. doi:10.1016/j.tibs.2015.03.001.
114. Karreth FA, Tay Y, Perna D, Ala U, Tan SM, Rust AG, et al. In vivo identification of tumor-suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell (2011) 147:382-95. doi:10.1016/j.cell.2011.09.032.
115. Lee JO, Yang H, Georgescu MM, Di Cristofano A, Maehama T, Shi Y, et al. Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association. Cell (1999) 99:323-34. doi:10.1016/S0092-8674(00)81663-3.
116. Silva A, Yunes JA, Cardoso BA, Martins LR, Jotta PY, Abecasis M, et al. PTEN posttranslational inactivation and hyperactivation of the PI3K/Akt pathway sustain primary T cell leukemia viability. J Clin Invest (2008) 118:3762-74. doi:10.1172/JCI34616.
117. Nakahata S, Ichikawa T, Maneesaay P, Saito Y, Nagai K, Tamura T, et al. Loss of NDRG2 expression activates PI3K-AKT signalling via PTEN phosphorylation in ATLL and other cancers. Nat Commun (2014) 5:3393. doi:10.1038/ncomms4393.
118. Yang Z, Yuan XG, Chen J, Luo SW, Luo ZJ, Lu NH. Reduced expression of PTEN and increased PTEN phosphorylation at residue Ser380 in gastric cancer tissues: a novel mechanism of PTEN inactivation. Clin Res Hepatol Gastroenterol (2013) 37:72-9. doi:10.1016/j.clinre.2012.03.002.
119. Al-Khouri AM, Ma Y, Togo SH, Williams S, Mustelin T. Cooperative phosphorylation of the tumor suppressor phosphatase and tensin homologue (PTEN) by casein kinases and glycogen synthase kinase 3beta. J Biol Chem (2005) 280:35195-202. doi:10.1074/jbc.M503045200.
120. Xu D, Yao Y, Jiang X, Lu L, Dai W. Regulation of PTEN stability and activity by Plk3. J Biol Chem (2010) 285:39935-42. doi:10.1074/jbc.M110.166462.
121. Vazquez F, Ramaswamy S, Nakamura N, Sellers WR. Phosphorylation of the PTEN tail regulates protein stability and function. Mol Cell Biol (2000) 20:5010-8. doi:10.1128/MCB.20.14.5010-5018.2000.
122. Torres J, Pulido R. The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus. Implications for PTEN stability to proteasome-mediated degradation. J Biol Chem (2001) 276:993-8. doi:10.1074/jbc.M009134200.
123. Wu Y, Zhou H, Wu K, Lee S, Li R, Liu X. PTEN phosphorylation and nuclear export mediate free fatty acid-induced oxidative stress. Antioxid Redox Signal (2014) 20:1382-95. doi:10.1089/ars.2013.5498.
124. Maccario H, Perera NM, Davidson L, Downes CP, Leslie NR. PTEN is destabilized by phosphorylation on Thr366. Biochem J (2007) 405:439-44. doi:10.1042/BJ20061837.
125. Xu D, Yao Y, Lu L, Costa M, Dai W. Plk3 functions as an essential component of the hypoxia regulatory pathway by direct phosphorylation of HIF-1alpha. J Biol Chem (2010) 285:38944-50. doi:10.1074/jbc.M110.160325.
126. Das S, Dixon JE, Cho W. Membrane-binding and activation mechanism of PTEN. Proc Natl Acad Sci U S A (2003) 100:7491-6. doi:10.1073/pnas.0932835100.
127. Vazquez F, Matsuoka S, Sellers WR, Yanagida T, Ueda M, Devreotes PN. Tumor suppressor PTEN acts through dynamic interaction with the plasma membrane. Proc Natl Acad Sci U S A (2006) 103:3633-8. doi:10.1073/pnas.0510570103.
128. Rahdar M, Inoue T, Meyer T, Zhang J, Vazquez F, Devreotes PN. A phosphorylation-dependent intramolecular interaction regulates the membrane association and activity of the tumor suppressor PTEN. Proc Natl Acad Sci U S A (2009) 106:480-5. doi:10.1073/pnas.0811212106.
129. Ross AH, Gericke A. Phosphorylation keeps PTEN phosphatase closed for business. Proc Natl Acad Sci U S A (2009) 106:1297-8. doi:10.1073/pnas.0812473106.
130. Bolduc D, Rahdar M, Tu-Sekine B, Sivakumaren SC, Raben D, Amzel LM, et al. Phosphorylation-mediated PTEN conformational closure and deactivation revealed with protein semisynthesis. Elife (2013) 2:e00691. doi:10.7554/eLife.00691.
131. Wu X, Hepner K, Castelino-Prabhu S, Do D, Kaye MB, Yuan XJ, et al. Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2. Proc Natl Acad Sci U S A (2000) 97:4233-8. doi:10.1073/pnas.97.8.4233.
132. Wu Y, Dowbenko D, Spencer S, Laura R, Lee J, Gu Q, et al. Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase. J Biol Chem (2000) 275:21477-85. doi:10.1074/jbc.M909741199.
133. Tolkacheva T, Boddapati M, Sanfiz A, Tsuchida K, Kimmelman AC, Chan AM. Regulation of PTEN binding to MAGI-2 by two putative phosphorylation sites at threonine 382 and 383. Cancer Res (2001) 61:4985-9.
134. Campbell RB, Liu F, Ross AH. Allosteric activation of PTEN phosphatase by phosphatidylinositol 4,5-bisphosphate. J Biol Chem (2003) 278:33617-20. doi:10.1074/jbc.C300296200.
135. Papa A, Wan L, Bonora M, Salmena L, Song MS, Hobbs RM, et al. Cancer-associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function. Cell (2014) 157:595-610. doi:10.1016/j.cell.2014.03.027.
136. Gil A, Andres-Pons A, Fernandez E, Valiente M, Torres J, Cervera J, 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. Mol Biol Cell (2006) 17:4002-13. doi:10.1091/mbc.E06-05-0380.
137. Li Z, Dong X, Wang Z, Liu W, Deng N, Ding Y, et al. Regulation of PTEN by Rho small GTPases. Nat Cell Biol (2005) 7:399-404. doi:10.1038/ncb1236.
138. Yim EK, Peng G, Dai H, Hu R, Li K, Lu Y, et al. Rak functions as a tumor suppressor by regulating PTEN protein stability and function. Cancer Cell (2009) 15:304-14. doi:10.1016/j.ccr.2009.02.012.
139. Eickholt BJ, Ahmed AI, Davies M, Papakonstanti EA, Pearce W, Starkey ML, et al. Control of axonal growth and regeneration of sensory neurons by the p110d PI 3-kinase. PLoS One (2007) 2:e869. doi:10.1371/journal.pone.0000869.
140. Papakonstanti EA, Ridley AJ, Vanhaesebroeck B. The p110d isoform of PI 3-kinase negatively controls RhoA and PTEN. EMBO J (2007) 26:3050-61. doi:10.1038/sj.emboj.7601763.
141. Tzenaki N, Aivaliotis M, Papakonstanti EA. FAK phosphorylates PTEN under the control of p110d PI3 kinase. FASEB J (2015).
142. Raftopoulou M, Etienne-Manneville S, Self A, Nicholls S, Hall A. Regulation of cell migration by the C2 domain of the tumor suppressor PTEN. Science (2004) 303:1179-81. doi:10.1126/science.1092089.
143. Tibarewal P, Zilidis G, Spinelli L, Schurch N, Maccario H, Gray A, et al. PTEN protein phosphatase activity correlates with control of gene expression and invasion, a tumor-suppressing phenotype, but not with AKT activity. Sci Signal (2012) 5:ra18. doi:10.1126/scisignal.2002138.
144. Cho SH, Lee CH, Ahn Y, Kim H, Kim H, Ahn CY, et al. Redox regulation of PTEN and protein tyrosine phosphatases in H(2)O(2) mediated cell signaling. FEBS Lett (2004) 560:7-13. doi:10.1016/S0014-5793(04)00112-7.
145. Leslie NR, Bennett D, Lindsay YE, Stewart H, Gray A, Downes CP. Redox regulation of PI 3-kinase signalling via inactivation of PTEN. EMBO J (2003) 22:5501-10. doi:10.1093/emboj/cdg513.
146. Cao J, Schulte J, Knight A, Leslie NR, Zagozdzon A, Bronson R, et al. Prdx1 inhibits tumorigenesis via regulating PTEN/AKT activity. EMBO J (2009) 28:1505-17. doi:10.1038/emboj.2009.101.
147. Lee SR, Yang KS, Kwon J, Lee C, Jeong W, Rhee SG. Reversible inactivation of the tumor suppressor PTEN by H2O2. J Biol Chem (2002) 277:20336-42. doi:10.1074/jbc.M111899200.
148. Hui ST, Andres AM, Miller AK, Spann NJ, Potter DW, Post NM, et al. Txnip balances metabolic and growth signaling via PTEN disulfide reduction. Proc Natl Acad Sci U S A (2008) 105:3921-6. doi:10.1073/pnas.0800293105.
149. Meuillet EJ, Mahadevan D, Berggren M, Coon A, Powis G. Thioredoxin-1 binds to the C2 domain of PTEN inhibiting PTEN's lipid phosphatase activity and membrane binding: a mechanism for the functional loss of PTEN's tumor suppressor activity. Arch Biochem Biophys (2004) 429:123-33. doi:10.1016/j.abb.2004.04.020.
150. Okumura K, Mendoza M, Bachoo RM, Depinho RA, Cavenee WK, Furnari FB. PCAF modulates PTEN activity. J Biol Chem (2006) 281:26562-8. doi:10.1074/jbc.M605391200.
151. Ding L, Chen S, Liu P, Pan Y, Zhong J, Regan KM, et al. CBP loss cooperates with PTEN haploinsufficiency to drive prostate cancer: implications for epigenetic therapy. Cancer Res (2014) 74:2050-61. doi:10.1158/0008-5472.CAN-13-1659.
152. Chae HD, Broxmeyer HE. SIRT1 deficiency downregulates PTEN/JNK/FOXO1 pathway to block reactive oxygen species-induced apoptosis in mouse embryonic stem cells. Stem Cells Dev (2011) 20:1277-85. doi:10.1089/scd.2010.0465.
153. Trotman LC, Wang X, Alimonti A, Chen Z, Teruya-Feldstein J, Yang H, et al. Ubiquitination regulates PTEN nuclear import and tumor suppression. Cell (2007) 128:141-56. doi:10.1016/j.cell.2006.11.040.
154. Wang X, Trotman LC, Koppie T, Alimonti A, Chen Z, Gao Z, et al. NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN. Cell (2007) 128:129-39. doi:10.1016/j.cell.2006.11.039.
155. Amodio N, Scrima M, Palaia L, Salman AN, Quintiero A, Franco R, et al. Oncogenic role of the E3 ubiquitin ligase NEDD4-1, a PTEN negative regulator, in non-small-cell lung carcinomas. Am J Pathol (2010) 177:2622-34. doi:10.2353/ajpath.2010.091075.
156. Fouladkou F, Landry T, Kawabe H, Neeb A, Lu C, Brose N, et al. The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization. Proc Natl Acad Sci U S A (2008) 105:8585-90. doi:10.1073/pnas.0803233105.
157. Eide PW, Cekaite L, Danielsen SA, Eilertsen IA, Kjenseth A, Fykerud TA, et al. NEDD4 is overexpressed in colorectal cancer and promotes colonic cell growth independently of the PI3K/PTEN/AKT pathway. Cell Signal (2013) 25:12-8. doi:10.1016/j.cellsig.2012.08.012.
158. van Themsche C, Leblanc V, Parent S, Asselin E. X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization. J Biol Chem (2009) 284:20462-6. doi:10.1074/jbc.C109.009522.
159. Maddika S, Kavela S, Rani N, Palicharla VR, Pokorny JL, Sarkaria JN, et al. WWP2 is an E3 ubiquitin ligase for PTEN. Nat Cell Biol (2011) 13:728-33. doi:10.1038/ncb2240.
160. Lee JT, Shan J, Zhong J, Li M, Zhou B, Zhou A, et al. RFP-mediated ubiquitination of PTEN modulates its effect on AKT activation. Cell Res (2013) 23:552-64. doi:10.1038/cr.2013.27.
161. Ahmed SF, Deb S, Paul I, Chatterjee A, Mandal T, Chatterjee U, et al. The chaperone-assisted E3 ligase C terminus of Hsc70-interacting protein (CHIP) targets PTEN for proteasomal degradation. J Biol Chem (2012) 287:15996-6006. doi:10.1074/jbc.M111.321083.
162. Song MS, Salmena L, Carracedo A, Egia A, Lo-Coco F, Teruya-Feldstein J, et al. The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network. Nature (2008) 455:813-7. doi:10.1038/nature07290.
163. Gonzalez-Santamaria J, Campagna M, Ortega-Molina A, Marcos-Villar L, De La Cruz-Herrera CF, Gonzalez D, et al. Regulation of the tumor suppressor PTEN by SUMO. Cell Death Dis (2012) 3:e393. doi:10.1038/cddis.2012.135.
164. Huang J, Yan J, Zhang J, Zhu S, Wang Y, Shi T, et al. SUMO1 modification of PTEN regulates tumorigenesis by controlling its association with the plasma membrane. Nat Commun (2012) 3:911. doi:10.1038/ncomms1919.
165. Bassi C, Ho J, Srikumar T, Dowling RJ, Gorrini C, Miller SJ, et al. Nuclear PTEN controls DNA repair and sensitivity to genotoxic stress. Science (2013) 341:395-9. doi:10.1126/science.1236188.
166. Sanchez T, Thangada S, Wu MT, Kontos CD, Wu D, Wu H, et al. PTEN as an effector in the signaling of antimigratory G protein-coupled receptor. Proc Natl Acad Sci U S A (2005) 102:4312-7. doi:10.1073/pnas.0409784102.
167. Cao J, Wan L, Hacker E, Dai X, Lenna S, Jimenez-Cervantes C, et al. MC1R is a potent regulator of PTEN after UV exposure in melanocytes. Mol Cell (2013) 51:409-22. doi:10.1016/j.molcel.2013.08.010.
168. Lin HK, Hu YC, Lee DK, Chang C. Regulation of androgen receptor signaling by PTEN (phosphatase and tensin homolog deleted on chromosome 10) tumor suppressor through distinct mechanisms in prostate cancer cells. Mol Endocrinol (2004) 18:2409-23. doi:10.1210/me.2004-0117.
169. Rosenkranz AA, Slastnikova TA, Durymanov MO, Sobolev AS. Malignant melanoma and melanocortin 1 receptor. Biochemistry (Mosc) (2013) 78:1228-37. doi:10.1134/S0006297913110035.
170. He L, Fan C, Kapoor A, Ingram AJ, Rybak AP, Austin RC, et al. Alpha-mannosidase 2C1 attenuates PTEN function in prostate cancer cells. Nat Commun (2011) 2:307. doi:10.1038/ncomms1309.
171. Gorbenko O, Panayotou G, Zhyvoloup A, Volkova D, Gout I, Filonenko V. Identification of novel PTEN-binding partners: PTEN interaction with fatty acid binding protein FABP4. Mol Cell Biochem (2010) 337:299-305. doi:10.1007/s11010-009-0312-1.
172. van Diepen MT, Parsons M, Downes CP, Leslie NR, Hindges R, Eickholt BJ. MyosinV controls PTEN function and neuronal cell size. Nat Cell Biol (2009) 11:1191-6. doi:10.1038/ncb1961.
173. Mistafa O, Ghalali A, Kadekar S, Hogberg J, Stenius U. Purinergic receptor-mediated rapid depletion of nuclear phosphorylated Akt depends on pleckstrin homology domain leucine-rich repeat phosphatase, calcineurin, protein phosphatase 2A, and PTEN phosphatases. J Biol Chem (2010) 285:27900-10. doi:10.1074/jbc.M110.117093.
174. von Stein W, Ramrath A, Grimm A, Muller-Borg M, Wodarz A. Direct association of Bazooka/PAR-3 with the lipid phosphatase PTEN reveals a link between the PAR/aPKC complex and phosphoinositide signaling. Development (2005) 132:1675-86. doi:10.1242/dev.01720.
175. Tamura M, Gu J, Danen EHJ, Takino T, Miyamoto S, Yamada KM. PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3-kinase/Akt cell survival pathway. J Biol Chem (1999) 274:20693-703. doi:10.1074/jbc.274.29.20693.
176. Haier J, Nicolson GL. PTEN regulates tumor cell adhesion of colon carcinoma cells under dynamic conditions of fluid flow. Oncogene (2002) 21:1450-60. doi:10.1038/sj.onc.1205213.
177. Mehenni H, Lin-Marq N, Buchet-Poyau K, Reymond A, Collart MA, Picard D, et al. LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes. Hum Mol Genet (2005) 14:2209-19. doi:10.1093/hmg/ddi225.
178. Li Z, Jiang H, Xie W, Zhang Z, Smrcka AV, Wu D. Roles of PLC-b2 and-b3 and PI3Kg in chemoattractant-mediated signal transduction. Science (2000) 287:1046-9. doi:10.1126/science.287.5455.1046.
179. Kotelevets L, Van Hengel J, Bruyneel E, Mareel M, Van Roy F, Chastre E. Implication of the MAGI-1b/PTEN signalosome in stabilization of adherens junctions and suppression of invasiveness. FASEB J (2005) 19:115-7. doi:10.1096/fj.04-1942fje.
180. Sotelo NS, Valiente M, Gil A, Pulido R. A functional network of the tumor suppressors APC, hDlg, and PTEN, that relies on recognition of specific PDZ-domains. J Cell Biochem (2012) 113:2661-70. doi:10.1002/jcb.24141.
181. Adey NB, Huang L, Ormonde PA, Baumgard ML, Pero R, Byreddy DV, et al. Threonine phosphorylation of the MMAC1/PTEN PDZ binding domain both inhibits and stimulates PDZ binding. Cancer Res (2000) 60:35-7.
182. Valiente M, Andres-Pons A, Gomar B, Torres J, Gil A, Tapparel C, et al. Binding of PTEN to specific PDZ domains contributes to PTEN protein stability and phosphorylation by microtubule-associated serine/threonine kinases. J Biol Chem (2005) 280:28936-43. doi:10.1074/jbc.M504761200.
183. Caselli A, Mazzinghi B, Camici G, Manao G, Ramponi G. Some protein tyrosine phosphatases target in part to lipid rafts and interact with caveolin-1. Biochem Biophys Res Commun (2002) 296:692-7. doi:10.1016/S0006-291X(02)00928-2.
184. Lin MC, Liu YC, Tam MF, Lu YJ, Hsieh YT, Lin LY. PTEN interacts with metal-responsive transcription factor 1 and stimulates its transcriptional activity. Biochem J (2012) 441:367-77. doi:10.1042/BJ20111257.
185. Freeman DJ, Li AG, Wei G, Li HH, Kertesz N, Lesche R, et al. PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and-independent mechanisms. Cancer Cell (2003) 3:117-30. doi:10.1016/S1535-6108(03)00021-7.
186. Yang C, Li S, Wang M, Chang AK, Liu Y, Zhao F, et al. PTEN suppresses the oncogenic function of AIB1 through decreasing its protein stability via mechanism involving Fbw7 alpha. Mol Cancer (2013) 12:21. doi:10.1186/1476-4598-12-21.
187. Teicher BA. Transforming growth factor-beta and the immune response to malignant disease. Clin Cancer Res (2007) 13:6247-51. doi:10.1158/1078-0432.CCR-07-1654.
188. Hjelmeland AB, Hjelmeland MD, Shi Q, Hart JL, Bigner DD, Wang XF, et al. Loss of phosphatase and tensin homologue increases transforming growth factor beta-mediated invasion with enhanced SMAD3 transcriptional activity. Cancer Res (2005) 65:11276-81. doi:10.1158/0008-5472.CAN-05-3016.
189. Fan C, He L, Kapoor A, Rybak AP, De Melo J, Cutz JC, et al. PTEN inhibits BMI1 function independently of its phosphatase activity. Mol Cancer (2009) 8:98. doi:10.1186/1476-4598-8-98.
190. Kim YJ, Park SJ, Choi EY, Kim S, Kwak HJ, Yoo BC, et al. PTEN modulates miR-21 processing via RNA-regulatory protein RNH1. PLoS One (2011) 6:e28308. doi:10.1371/journal.pone.0028308.
191. Shen WH, Balajee AS, Wang J, Wu H, Eng C, Pandolfi PP, et al. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell (2007) 128:157-70. doi:10.1016/j.cell.2006.11.042.
192. Li M, Zhang P. The function of APC/CCdh1 in cell cycle and beyond. Cell Div (2009) 4:2. doi:10.1186/1747-1028-4-2.
193. Song MS, Carracedo A, Salmena L, Song SJ, Egia A, Malumbres M, et al. Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner. Cell (2011) 144:187-99. doi:10.1016/j.cell.2010.12.020.
194. He L, Ingram A, Rybak AP, Tang D. Shank-interacting protein-like 1 promotes tumorigenesis via PTEN inhibition in human tumor cells. J Clin Invest (2010) 120:2094-108. doi:10.1172/JCI40778.
195. Okahara F, Ikawa H, Kanaho Y, Maehama T. Regulation of PTEN phosphorylation and stability by a tumor suppressor candidate protein. J Biol Chem (2004) 279:45300-3. doi:10.1074/jbc.C400377200.
196. Bononi A, Pinton P. Study of PTEN subcellular localization. Methods (2015) 7(7-78):92-103. doi:10.1016/j.ymeth.2014.10.002.
197. Walker SM, Leslie NR, Perera NM, Batty IH, Downes CP. The tumour-suppressor function of PTEN requires an N-terminal lipid-binding motif. Biochem J (2004) 379:301-7. doi:10.1042/BJ20031839.
198. Redfern RE, Redfern D, Furgason ML, Munson M, Ross AH, Gericke A. PTEN phosphatase selectively binds phosphoinositides and undergoes structural changes. Biochemistry (2008) 47:2162-71. doi:10.1021/bi702114w.
199. Niedermeier M, Hennessy BT, Knight ZA, Henneberg M, Hu J, Kurtova AV, et al. Isoform-selective phosphoinositide 3'-kinase inhibitors inhibit CXCR4 signaling and overcome stromal cell-mediated drug resistance in chronic lymphocytic leukemia: a novel therapeutic approach. Blood (2009) 113:5549-57. doi:10.1182/blood-2008-06-165068.
200. Lindsay Y, Mccoull D, Davidson L, Leslie NR, Fairservice A, Gray A, et al. Localization of agonist-sensitive PtdIns(3,4,5)P3 reveals a nuclear pool that is insensitive to PTEN expression. J Cell Sci (2006) 119:5160-8. doi:10.1242/jcs.000133.
201. Li P, Wang D, Li H, Yu Z, Chen X, Fang J. Identification of nucleolus-localized PTEN and its function in regulating ribosome biogenesis. Mol Biol Rep (2014) 41:6383-90. doi:10.1007/s11033-014-3518-6.
202. Denning G, Jean-Joseph B, Prince C, Durden DL, Vogt PK. A short N-terminal sequence of PTEN controls cytoplasmic localization and is required for suppression of cell growth. Oncogene (2007) 26:3930-40. doi:10.1038/sj.onc.1210175.
203. Mossink MH, Van Zon A, Scheper RJ, Sonneveld P, Wiemer EA. Vaults: a ribonucleoprotein particle involved in drug resistance? Oncogene (2003) 22:7458-67. doi:10.1038/sj.onc.1206947.
204. Yu Z, Fotouhi-Ardakani N, Wu L, Maoui M, Wang S, Banville D, et al. PTEN associates with the vault particles in HeLa cells. J Biol Chem (2002) 277:40247-52. doi:10.1074/jbc.M207608200.
205. Chung JH, Ginn-Pease ME, Eng C. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) has nuclear localization signal-like sequences for nuclear import mediated by major vault protein. Cancer Res (2005) 65:4108-16. doi:10.1158/0008-5472.CAN-05-0124.
206. Liu F, Wagner S, Campbell RB, Nickerson JA, Schiffer CA, Ross AH. PTEN enters the nucleus by diffusion. J Cell Biochem (2005) 96:221-34. doi:10.1002/jcb.20525.
207. Liang H, He S, Yang J, Jia X, Wang P, Chen X, et al. PTENalpha, a PTEN isoform translated through alternative initiation, regulates mitochondrial function and energy metabolism. Cell Metab (2014) 19:836-48. doi:10.1016/j.cmet.2014.03.023.
208. Zhu Y, Hoell P, Ahlemeyer B, Krieglstein J. PTEN: a crucial mediator of mitochondria-dependent apoptosis. Apoptosis (2006) 11:197-207. doi:10.1007/s10495-006-3714-5.
209. Bononi A, Bonora M, Marchi S, Missiroli S, Poletti F, Giorgi C, et al. Identification of PTEN at the ER and MAMs and its regulation of Ca(2+) signaling and apoptosis in a protein phosphatase-dependent manner. Cell Death Differ (2013) 20:1631-43. doi:10.1038/cdd.2013.77.
210. Patergnani S, Suski JM, Agnoletto C, Bononi A, Bonora M, De Marchi E, et al. Calcium signaling around mitochondria associated membranes (MAMs). Cell Commun Signal (2011) 9:19. doi:10.1186/1478-811X-9-19.
211. Giorgi C, Baldassari F, Bononi A, Bonora M, De Marchi E, Marchi S, et al. Mitochondrial Ca(2+) and apoptosis. Cell Calcium (2012) 52:36-43. doi:10.1016/j.ceca.2012.02.008.
212. Hopkins BD, Fine B, Steinbach N, Dendy M, Rapp Z, Shaw J, et al. A secreted PTEN phosphatase that enters cells to alter signaling and survival. Science (2013) 341:399-402. doi:10.1126/science.1234907.
213. Putz U, Howitt J, Doan A, Goh CP, Low LH, Silke J, et al. The tumor suppressor PTEN is exported in exosomes and has phosphatase activity in recipient cells. Sci Signal (2012) 5:ra70. doi:10.1126/scisignal.2003084.
214. Howitt J, Lackovic J, Low LH, Naguib A, Macintyre A, Goh CP, et al. Ndfip1 regulates nuclear Pten import in vivo to promote neuronal survival following cerebral ischemia. J Cell Biol (2012) 196:29-36. doi:10.1083/jcb.201105009.