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PMID: 22473468 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

The functions and regulation of the PTEN tumour suppressor.

Nature reviews. Molecular cell biology ·Vol. 13 ·No. 5 ·2012-04-04 ·Pages 283-96

Song MS, Salmena L, Pandolfi PP

Abstract

The importance of the physiological function of phosphatase and tensin homologue (PTEN) is illustrated by its frequent disruption in cancer. By suppressing the phosphoinositide 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) pathway through its lipid phosphatase activity, PTEN governs a plethora of cellular processes including survival, proliferation, energy metabolism and cellular architecture. Consequently, mechanisms regulating PTEN expression and function, including transcriptional regulation, post-transcriptional regulation by non-coding RNAs, post-translational modifications and protein-protein interactions, are all altered in cancer. The repertoire of PTEN functions has recently been expanded to include phosphatase-independent activities and crucial functions within the nucleus. Our increasing knowledge of PTEN and pathologies in which its function is altered will undoubtedly inform the rational design of novel therapies.

MeSH Terms
Animals Cell Nucleus/enzymology Gene Expression Regulation Humans Mutation Neoplasms/enzymology,pathology Neoplastic Stem Cells/enzymology,physiology PTEN Phosphohydrolase/genetics,metabolism,physiology Protein Conformation Signal Transduction Tumor Suppressor Proteins/genetics,metabolism,physiology
Chemicals
Tumor Suppressor Proteins PTEN Phosphohydrolase PTEN protein, human
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Song Min Sup
Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Harvard Medical School, Boston, Massachuchetts 02215, USA. [email protected]
Salmena Leonardo
Pandolfi Pier Paolo
References (160)
160 references, click to expand
  1. PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway.
    Proc Natl Acad Sci U S A. 1999 May 25;96(11):6199-204 PMID: 10339565
  2. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN.
    Cell. 1998 Oct 2;95(1):29-39 PMID: 9778245
  3. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate.
    J Biol Chem. 1998 May 29;273(22):13375-8 PMID: 9593664
  4. Regulation of PTEN phosphorylation and stability by a tumor suppressor candidate protein.
    J Biol Chem. 2004 Oct 29;279(44):45300-3 PMID: 15355975
  5. Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs.
    Cell. 2011 Oct 14;147(2):344-57 PMID: 22000013
  6. Id-1 activates Akt-mediated Wnt signaling and p27(Kip1) phosphorylation through PTEN inhibition.
    Oncogene. 2009 Feb 12;28(6):824-31 PMID: 19079342
  7. Cooperative phosphorylation of the tumor suppressor phosphatase and tensin homologue (PTEN) by casein kinases and glycogen synthase kinase 3beta.
    J Biol Chem. 2005 Oct 21;280(42):35195-202 PMID: 16107342
  8. The Catalogue of Somatic Mutations in Cancer (COSMIC).
    Curr Protoc Hum Genet. 2008 Apr;Chapter 10:Unit 10.11 PMID: 18428421
  9. Genetic deletion of the Pten tumor suppressor gene promotes cell motility by activation of Rac1 and Cdc42 GTPases.
    Curr Biol. 2000 Apr 6;10(7):401-4 PMID: 10753747
  10. Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence.
    Nature. 2001 Feb 22;409(6823):1067-70 PMID: 11234019
  11. PTEN, more than the AKT pathway.
    Carcinogenesis. 2007 Jul;28(7):1379-86 PMID: 17341655
  12. CREB is a novel nuclear target of PTEN phosphatase.
    Cancer Res. 2011 Apr 15;71(8):2821-5 PMID: 21385900
  13. Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1alpha transcription coactivator.
    Nature. 2007 Jun 21;447(7147):1012-6 PMID: 17554339
  14. Repression of PTEN phosphatase by Snail1 transcriptional factor during gamma radiation-induced apoptosis.
    Mol Cell Biol. 2008 Mar;28(5):1528-40 PMID: 18172008
  15. Reversible inactivation of the tumor suppressor PTEN by H2O2.
    J Biol Chem. 2002 Jun 7;277(23):20336-42 PMID: 11916965
  16. Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate.
    Nat Genet. 2009 May;41(5):619-24 PMID: 19396168
  17. A continuum model for tumour suppression.
    Nature. 2011 Aug 10;476(7359):163-9 PMID: 21833082
  18. Txnip balances metabolic and growth signaling via PTEN disulfide reduction.
    Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3921-6 PMID: 18322014
  19. Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling.
    Science. 2011 Jun 10;332(6035):1322-6 PMID: 21659605
  20. Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse.
    Nat Genet. 2001 Feb;27(2):222-4 PMID: 11175795
  21. α-Mannosidase 2C1 attenuates PTEN function in prostate cancer cells.
    Nat Commun. 2011;2:307 PMID: 21556061
  22. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology.
    Nature. 2010 Jun 24;465(7301):1033-8 PMID: 20577206
  23. WWP2 is an E3 ubiquitin ligase for PTEN.
    Nat Cell Biol. 2011 Jun;13(6):728-33 PMID: 21532586
  24. Negative regulation of neural stem/progenitor cell proliferation by the Pten tumor suppressor gene in vivo.
    Science. 2001 Dec 7;294(5549):2186-9 PMID: 11691952
  25. Cooperativity of TMPRSS2-ERG with PI3-kinase pathway activation in prostate oncogenesis.
    Nat Genet. 2009 May;41(5):524-6 PMID: 19396167
  26. The ER UDPase ENTPD5 promotes protein N-glycosylation, the Warburg effect, and proliferation in the PTEN pathway.
    Cell. 2010 Nov 24;143(5):711-24 PMID: 21074248
  27. Protein interactions of phosphatase and tensin homologue (PTEN) and its cancer-associated G20E mutant compared by using stable isotope labeling by amino acids in cell culture-based parallel affinity purification.
    J Biol Chem. 2011 May 20;286(20):18093-103 PMID: 21454687
  28. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer.
    Science. 1997 Mar 28;275(5308):1943-7 PMID: 9072974
  29. Lack of PTEN sequesters CHK1 and initiates genetic instability.
    Cancer Cell. 2005 Feb;7(2):193-204 PMID: 15710331
  30. In vivo identification of tumor- suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma.
    Cell. 2011 Oct 14;147(2):382-95 PMID: 22000016
  31. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes.
    Nat Immunol. 2008 Apr;9(4):405-14 PMID: 18327259
  32. Distinct epigenetic changes in the stromal cells of breast cancers.
    Nat Genet. 2005 Aug;37(8):899-905 PMID: 16007089
  33. Full intracellular retention of GLUT4 requires AS160 Rab GTPase activating protein.
    Cell Metab. 2005 Oct;2(4):263-72 PMID: 16213228
  34. SIRT1 deficiency downregulates PTEN/JNK/FOXO1 pathway to block reactive oxygen species-induced apoptosis in mouse embryonic stem cells.
    Stem Cells Dev. 2011 Jul;20(7):1277-85 PMID: 21083429
  35. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer.
    J Clin Invest. 2008 Sep;118(9):3065-74 PMID: 18725988
  36. Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40.
    Nat Cell Biol. 2007 Mar;9(3):316-23 PMID: 17277771
  37. Shank-interacting protein-like 1 promotes tumorigenesis via PTEN inhibition in human tumor cells.
    J Clin Invest. 2010 Jun;120(6):2094-108 PMID: 20458142
  38. Ubiquitination regulates PTEN nuclear import and tumor suppression.
    Cell. 2007 Jan 12;128(1):141-56 PMID: 17218261
  39. Fibroblasts in cancer.
    Nat Rev Cancer. 2006 May;6(5):392-401 PMID: 16572188
  40. PTEN-mediated apical segregation of phosphoinositides controls epithelial morphogenesis through Cdc42.
    Cell. 2007 Jan 26;128(2):383-97 PMID: 17254974
  41. Stem cell factor SALL4 represses the transcriptions of PTEN and SALL1 through an epigenetic repressor complex.
    PLoS One. 2009;4(5):e5577 PMID: 19440552
  42. Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR.
    J Clin Invest. 2003 Oct;112(8):1223-33 PMID: 14561707
  43. Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2.
    Genes Dev. 2005 Aug 1;19(15):1773-8 PMID: 16027169
  44. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome.
    Nat Genet. 1997 May;16(1):64-7 PMID: 9140396
  45. E3 ligase Nedd4 promotes axon branching by downregulating PTEN.
    Neuron. 2010 Feb 11;65(3):341-57 PMID: 20159448
  46. Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism.
    Oncogene. 2007 Mar 22;26(13):1932-40 PMID: 17001314
  47. Mammalian target of rapamycin (mTOR) inhibition activates phosphatidylinositol 3-kinase/Akt by up-regulating insulin-like growth factor-1 receptor signaling in acute myeloid leukemia: rationale for therapeutic inhibition of both pathways.
    Blood. 2008 Jan 1;111(1):379-82 PMID: 17878402
  48. mTOR activation induces tumor suppressors that inhibit leukemogenesis and deplete hematopoietic stem cells after Pten deletion.
    Cell Stem Cell. 2010 Nov 5;7(5):593-605 PMID: 21040901
  49. Patterns of the early, gross chromosomal changes in malignant human gliomas.
    Hereditas. 1984;101(1):103-13 PMID: 6490389
  50. Tumor suppressor and anti-inflammatory actions of PPARgamma agonists are mediated via upregulation of PTEN.
    Curr Biol. 2001 May 15;11(10):764-8 PMID: 11378386
  51. Regulation of PTEN transcription by p53.
    Mol Cell. 2001 Aug;8(2):317-25 PMID: 11545734
  52. Pten in stromal fibroblasts suppresses mammary epithelial tumours.
    Nature. 2009 Oct 22;461(7267):1084-91 PMID: 19847259
  53. p85 Associates with unphosphorylated PTEN and the PTEN-associated complex.
    Mol Cell Biol. 2009 Oct;29(19):5377-88 PMID: 19635806
  54. PKB/AKT: functional insights from genetic models.
    Nat Rev Mol Cell Biol. 2001 Oct;2(10):760-8 PMID: 11584303
  55. The emerging mechanisms of isoform-specific PI3K signalling.
    Nat Rev Mol Cell Biol. 2010 May;11(5):329-41 PMID: 20379207
  56. Multi-genetic events collaboratively contribute to Pten-null leukaemia stem-cell formation.
    Nature. 2008 May 22;453(7194):529-33 PMID: 18463637
  57. PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention.
    Nature. 2006 May 25;441(7092):518-22 PMID: 16633340
  58. Differential requirement of mTOR in postmitotic tissues and tumorigenesis.
    Sci Signal. 2009 Jan 27;2(55):ra2 PMID: 19176516
  59. The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling.
    Science. 2011 Jun 10;332(6035):1317-22 PMID: 21659604
  60. DJ-1, a novel regulator of the tumor suppressor PTEN.
    Cancer Cell. 2005 Mar;7(3):263-73 PMID: 15766664
  61. Oxidation of DJ-1-dependent cell transformation through direct binding of DJ-1 to PTEN.
    Int J Oncol. 2009 Dec;35(6):1331-41 PMID: 19885556
  62. Defining the role of mTOR in cancer.
    Cancer Cell. 2007 Jul;12(1):9-22 PMID: 17613433
  63. Regulation of PTEN stability and activity by Plk3.
    J Biol Chem. 2010 Dec 17;285(51):39935-42 PMID: 20940307
  64. Pten is essential for embryonic development and tumour suppression.
    Nat Genet. 1998 Aug;19(4):348-55 PMID: 9697695
  65. Understanding the Warburg effect: the metabolic requirements of cell proliferation.
    Science. 2009 May 22;324(5930):1029-33 PMID: 19460998
  66. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis.
    Nature. 2005 Aug 4;436(7051):725-30 PMID: 16079851
  67. The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins.
    J Cell Biol. 2004 Jul 19;166(2):213-23 PMID: 15249583
  68. c-Jun promotes cellular survival by suppression of PTEN.
    Cell Death Differ. 2007 Feb;14(2):218-29 PMID: 16676006
  69. NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN.
    Cell. 2007 Jan 12;128(1):129-39 PMID: 17218260
  70. Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association.
    Cell. 1999 Oct 29;99(3):323-34 PMID: 10555148
  71. 4E-BP1 is a key effector of the oncogenic activation of the AKT and ERK signaling pathways that integrates their function in tumors.
    Cancer Cell. 2010 Jul 13;18(1):39-51 PMID: 20609351
  72. Activation of the PI3K pathway in cancer through inhibition of PTEN by exchange factor P-REX2a.
    Science. 2009 Sep 4;325(5945):1261-5 PMID: 19729658
  73. Localization of agonist-sensitive PtdIns(3,4,5)P3 reveals a nuclear pool that is insensitive to PTEN expression.
    J Cell Sci. 2006 Dec 15;119(Pt 24):5160-8 PMID: 17158918
  74. Constitutively active AKT depletes hematopoietic stem cells and induces leukemia in mice.
    Blood. 2010 Feb 18;115(7):1406-15 PMID: 20008787
  75. Essential role for nuclear PTEN in maintaining chromosomal integrity.
    Cell. 2007 Jan 12;128(1):157-70 PMID: 17218262
  76. Distinct functional outputs of PTEN signalling are controlled by dynamic association with β-arrestins.
    EMBO J. 2011 Jun 03;30(13):2557-68 PMID: 21642958
  77. Mutation and cancer: statistical study of retinoblastoma.
    Proc Natl Acad Sci U S A. 1971 Apr;68(4):820-3 PMID: 5279523
  78. Mitogen-activated protein kinase kinase-4 promotes cell survival by decreasing PTEN expression through an NF kappa B-dependent pathway.
    J Biol Chem. 2007 Feb 9;282(6):3507-19 PMID: 17158870
  79. The Egr-1 transcription factor directly activates PTEN during irradiation-induced signalling.
    Nat Cell Biol. 2001 Dec;3(12):1124-8 PMID: 11781575
  80. Regulation of cell migration by the C2 domain of the tumor suppressor PTEN.
    Science. 2004 Feb 20;303(5661):1179-81 PMID: 14976311
  81. Tenets of PTEN tumor suppression.
    Cell. 2008 May 2;133(3):403-14 PMID: 18455982
  82. 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 Dec;119(12):3626-36 PMID: 19884659
  83. PCAF modulates PTEN activity.
    J Biol Chem. 2006 Sep 8;281(36):26562-8 PMID: 16829519
  84. Pten regulates neuronal soma size: a mouse model of Lhermitte-Duclos disease.
    Nat Genet. 2001 Dec;29(4):404-11 PMID: 11726927
  85. Differential p53-independent outcomes of p19(Arf) loss in oncogenesis.
    Sci Signal. 2009 Aug 18;2(84):ra44 PMID: 19690330
  86. Evi1 represses PTEN expression and activates PI3K/AKT/mTOR via interactions with polycomb proteins.
    Blood. 2011 Mar 31;117(13):3617-28 PMID: 21289308
  87. Rak functions as a tumor suppressor by regulating PTEN protein stability and function.
    Cancer Cell. 2009 Apr 7;15(4):304-14 PMID: 19345329
  88. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer.
    Gastroenterology. 2007 Aug;133(2):647-58 PMID: 17681183
  89. Subtle variations in Pten dose determine cancer susceptibility.
    Nat Genet. 2010 May;42(5):454-8 PMID: 20400965
  90. Reprogramming of the tumour microenvironment by stromal PTEN-regulated miR-320.
    Nat Cell Biol. 2011 Dec 18;14(2):159-67 PMID: 22179046
  91. Tumours with PI3K activation are resistant to dietary restriction.
    Nature. 2009 Apr 9;458(7239):725-31 PMID: 19279572
  92. MyosinV controls PTEN function and neuronal cell size.
    Nat Cell Biol. 2009 Oct;11(10):1191-6 PMID: 19767745
  93. SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression.
    Nature. 2011 Feb 10;470(7333):269-73 PMID: 21289624
  94. Combating trastuzumab resistance by targeting SRC, a common node downstream of multiple resistance pathways.
    Nat Med. 2011 Apr;17(4):461-9 PMID: 21399647
  95. Form and function in protein dephosphorylation.
    Cell. 1996 Nov 1;87(3):361-4 PMID: 8898189
  96. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language?
    Cell. 2011 Aug 5;146(3):353-8 PMID: 21802130
  97. Dlg1-PTEN interaction regulates myelin thickness to prevent damaging peripheral nerve overmyelination.
    Science. 2010 Jun 11;328(5984):1415-8 PMID: 20448149
  98. Aberrant Rheb-mediated mTORC1 activation and Pten haploinsufficiency are cooperative oncogenic events.
    Genes Dev. 2008 Aug 15;22(16):2172-7 PMID: 18708577
  99. p19ARF links the tumour suppressor p53 to Ras.
    Nature. 1998 Sep 10;395(6698):125-6 PMID: 9744268
  100. Deletion of Pten in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte-Duclos disease.
    Nat Genet. 2001 Dec;29(4):396-403 PMID: 11726926
  101. An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma.
    Cell. 2011 Oct 14;147(2):370-81 PMID: 22000015
  102. Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner.
    Cell. 2011 Jan 21;144(2):187-99 PMID: 21241890
  103. In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics.
    Cell. 2011 Jun 24;145(7):1142-55 PMID: 21664664
  104. A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis.
    J Clin Invest. 2010 Mar;120(3):681-93 PMID: 20197621
  105. Pro-senescence therapy for cancer treatment.
    Nat Rev Cancer. 2011 Jun 24;11(7):503-11 PMID: 21701512
  106. MicroRNAs: target recognition and regulatory functions.
    Cell. 2009 Jan 23;136(2):215-33 PMID: 19167326
  107. miR-19 is a key oncogenic component of mir-17-92.
    Genes Dev. 2009 Dec 15;23(24):2839-49 PMID: 20008935
  108. PTEN loss in the continuum of common cancers, rare syndromes and mouse models.
    Nat Rev Cancer. 2011 Apr;11(4):289-301 PMID: 21430697
  109. Cellular transformation by the MSP58 oncogene is inhibited by its physical interaction with the PTEN tumor suppressor.
    Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2703-6 PMID: 15659546
  110. Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems.
    Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1563-8 PMID: 9990064
  111. Differential expression of novel naturally occurring splice variants of PTEN and their functional consequences in Cowden syndrome and sporadic breast cancer.
    Hum Mol Genet. 2006 Mar 1;15(5):777-87 PMID: 16436456
  112. Impaired Fas response and autoimmunity in Pten+/- mice.
    Science. 1999 Sep 24;285(5436):2122-5 PMID: 10497129
  113. Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas.
    Nat Genet. 2002 Nov;32(3):355-7 PMID: 12379854
  114. The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network.
    Nature. 2008 Oct 9;455(7214):813-7 PMID: 18716620
  115. Targeting AKT/mTOR and ERK MAPK signaling inhibits hormone-refractory prostate cancer in a preclinical mouse model.
    J Clin Invest. 2008 Sep;118(9):3051-64 PMID: 18725989
  116. PTEN, NHERF1 and PHLPP form a tumor suppressor network that is disabled in glioblastoma.
    Oncogene. 2012 Mar 8;31(10):1264-74 PMID: 21804599
  117. AKT/PKB signaling: navigating downstream.
    Cell. 2007 Jun 29;129(7):1261-74 PMID: 17604717
  118. P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase.
    Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9052-7 PMID: 9256433
  119. mTOR: from growth signal integration to cancer, diabetes and ageing.
    Nat Rev Mol Cell Biol. 2011 Jan;12(1):21-35 PMID: 21157483
  120. Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN.
    Science. 1998 Jun 5;280(5369):1614-7 PMID: 9616126
  121. The phosphoinositide 3-kinase regulatory subunit p85alpha can exert tumor suppressor properties through negative regulation of growth factor signaling.
    Cancer Res. 2010 Jul 1;70(13):5305-15 PMID: 20530665
  122. Polo-like kinase 1 facilitates loss of Pten tumor suppressor-induced prostate cancer formation.
    J Biol Chem. 2011 Oct 14;286(41):35795-35800 PMID: 21890624
  123. PTEN deficiency in endometrioid endometrial adenocarcinomas predicts sensitivity to PARP inhibitors.
    Sci Transl Med. 2010 Oct 13;2(53):53ra75 PMID: 20944090
  124. Identification of the JNK signaling pathway as a functional target of the tumor suppressor PTEN.
    Cancer Cell. 2007 Jun;11(6):555-69 PMID: 17560336
  125. Regulation of PTEN by Rho small GTPases.
    Nat Cell Biol. 2005 Apr;7(4):399-404 PMID: 15793569
  126. 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 Apr 11;97(8):4233-8 PMID: 10760291
  127. Germline PTEN promoter mutations and deletions in Cowden/Bannayan-Riley-Ruvalcaba syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase/Akt pathway.
    Am J Hum Genet. 2003 Aug;73(2):404-11 PMID: 12844284
  128. Phosphorylation of the PTEN tail acts as an inhibitory switch by preventing its recruitment into a protein complex.
    J Biol Chem. 2001 Dec 28;276(52):48627-30 PMID: 11707428
  129. The adaptor protein of the anaphase promoting complex Cdh1 is essential in maintaining replicative lifespan and in learning and memory.
    Nat Cell Biol. 2008 Sep;10(9):1083-9 PMID: 19160489
  130. Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas.
    J Clin Invest. 2004 Jun;113(12):1774-83 PMID: 15199412
  131. On respiratory impairment in cancer cells.
    Science. 1956 Aug 10;124(3215):269-70 PMID: 13351639
  132. Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling.
    Genes Dev. 2002 Oct 15;16(20):2627-32 PMID: 12381661
  133. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells.
    Nature. 2006 May 25;441(7092):475-82 PMID: 16598206
  134. Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors.
    EMBO Mol Med. 2009 Sep;1(6-7):315-22 PMID: 20049735
  135. mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs.
    Science. 2010 May 28;328(5982):1172-6 PMID: 20508131
  136. Prdx1 inhibits tumorigenesis via regulating PTEN/AKT activity.
    EMBO J. 2009 May 20;28(10):1505-17 PMID: 19369943
  137. Genetic dissection of the miR-17~92 cluster of microRNAs in Myc-induced B-cell lymphomas.
    Genes Dev. 2009 Dec 15;23(24):2806-11 PMID: 20008931
  138. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers.
    Nat Genet. 1997 Apr;15(4):356-62 PMID: 9090379
  139. Tumor suppression by PTEN requires the activation of the PKR-eIF2alpha phosphorylation pathway.
    Sci Signal. 2009 Dec 22;2(102):ra85 PMID: 20029030
  140. Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity.
    Nature. 2004 Sep 9;431(7005):200-5 PMID: 15306821
  141. PTEN loss compromises homologous recombination repair in astrocytes: implications for glioblastoma therapy with temozolomide or poly(ADP-ribose) polymerase inhibitors.
    Cancer Res. 2010 Jul 1;70(13):5457-64 PMID: 20530668
  142. Genetic dissection of the oncogenic mTOR pathway reveals druggable addiction to translational control via 4EBP-eIF4E.
    Cancer Cell. 2010 Mar 16;17(3):249-61 PMID: 20227039
  143. Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines.
    Gastroenterology. 2006 Jun;130(7):2113-29 PMID: 16762633
  144. Recombinant human erythropoietin antagonizes trastuzumab treatment of breast cancer cells via Jak2-mediated Src activation and PTEN inactivation.
    Cancer Cell. 2010 Nov 16;18(5):423-35 PMID: 21075308
  145. Direct positive regulation of PTEN by the p85 subunit of phosphatidylinositol 3-kinase.
    Proc Natl Acad Sci U S A. 2010 Mar 23;107(12):5471-6 PMID: 20212113
  146. A novel signaling network as a critical rheostat for the biology and maintenance of the normal stem cell and the cancer-initiating cell.
    Curr Opin Genet Dev. 2009 Feb;19(1):51-9 PMID: 19216069
  147. Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia.
    Nat Cell Biol. 2010 Apr;12(4):372-9 PMID: 20190740
  148. X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization.
    J Biol Chem. 2009 Jul 31;284(31):20462-6 PMID: 19473982
  149. Control of lipid metabolism by phosphorylation-dependent degradation of the SREBP family of transcription factors by SCF(Fbw7).
    Cell Metab. 2005 Jun;1(6):379-91 PMID: 16054087
  150. PTEN tumor suppressor associates with NHERF proteins to attenuate PDGF receptor signaling.
    EMBO J. 2006 Feb 22;25(4):910-20 PMID: 16456542
  151. The class III PI(3)K Vps34 promotes autophagy and endocytosis but not TOR signaling in Drosophila.
    J Cell Biol. 2008 May 19;181(4):655-66 PMID: 18474623
  152. PTEN: one gene, many syndromes.
    Hum Mutat. 2003 Sep;22(3):183-98 PMID: 12938083
  153. Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence.
    Nature. 2010 Mar 18;464(7287):374-9 PMID: 20237562
  154. The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization.
    Proc Natl Acad Sci U S A. 2008 Jun 24;105(25):8585-90 PMID: 18562292
  155. Molecular mechanisms of mTOR-mediated translational control.
    Nat Rev Mol Cell Biol. 2009 May;10(5):307-18 PMID: 19339977
  156. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism.
    Nat Rev Genet. 2006 Aug;7(8):606-19 PMID: 16847462
  157. PTEN posttranslational inactivation and hyperactivation of the PI3K/Akt pathway sustain primary T cell leukemia viability.
    J Clin Invest. 2008 Nov;118(11):3762-74 PMID: 18830414
  158. High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice.
    Curr Biol. 1998 Oct 22;8(21):1169-78 PMID: 9799734
  159. Loss of the miR-21 allele elevates the expression of its target genes and reduces tumorigenesis.
    Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10144-9 PMID: 21646541
  160. CBF-1 (RBP-J kappa) binds to the PTEN promoter and regulates PTEN gene expression.
    Cell Cycle. 2007 Jan 1;6(1):80-4 PMID: 17245125
Article Info
Journal
Nature reviews. Molecular cell biology
Abbr.
Nat Rev Mol Cell Biol
ISSN
1471-0080
DOI
10.1038/nrm3330
Email
[email protected]
Published
2012-04-04
Epub
2012-00-04
Pages
283-96
Language
English
Region
England
NLM ID
100962782
Subset
IM
Grants
NCI NIH HHS · R01 CA‑82328‑09 · United States
Canadian Institutes of Health Research · Canada
External Links
PubMed source DOI: 10.1038/nrm3330 View journal details
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