pten phosphohydrolase


Summary: A lipid phosphatase that contains a C2 DOMAIN and acts on phosphatidylinositol-3,4,5-trisphosphate to regulate various SIGNAL TRANSDUCTION PATHWAYS. It modulates CELL GROWTH PROCESSES; CELL MIGRATION; and APOPTOSIS. Mutations in PTEN are associated with COWDEN DISEASE and PROTEUS SYNDROME as well as NEOPLASTIC CELL TRANSFORMATION.

Top Publications

  1. Pilarski R, Burt R, Kohlman W, Pho L, Shannon K, Swisher E. Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria. J Natl Cancer Inst. 2013;105:1607-16 pubmed publisher
    ..Our goal was to develop revised, evidence-based diagnostic criteria and to include features of the broader spectrum of PTEN-related clinical syndromes...
  2. Li L, Li X, Wang L, Du W, Guo R, Liang H, et al. Matrine inhibits breast cancer growth via miR-21/PTEN/Akt pathway in MCF-7 cells. Cell Physiol Biochem. 2012;30:631-41 pubmed publisher
    ..Our findings also reinforce the notion that miRNAs can act as mediators of the therapeutic efficacy of natural medicines. ..
  3. Peifer M, Fernandez Cuesta L, Sos M, George J, Seidel D, Kasper L, et al. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet. 2012;44:1104-10 pubmed publisher
  4. Kalli A, Morgan G, Sansom M. Interactions of the auxilin-1 PTEN-like domain with model membranes result in nanoclustering of phosphatidyl inositol phosphates. Biophys J. 2013;105:137-45 pubmed publisher
    ..The interaction of membrane-bound auxilin-1 PTEN-like domain with negatively charged lipid headgroups results in nanoclustering of PIP2 molecules in the adjacent bilayer leaflet. ..
  5. Choucair K, Ejdelman J, Brimo F, Aprikian A, Chevalier S, Lapointe J. PTEN genomic deletion predicts prostate cancer recurrence and is associated with low AR expression and transcriptional activity. BMC Cancer. 2012;12:543 pubmed publisher
    ..Altogether, our data suggest that PTEN deleted tumors expressing low levels of AR may represent a worse prognostic subset of PCa establishing a challenge for therapeutic management. ..
  6. McMahon J, Huang X, Yang J, Komatsu M, Yue Z, Qian J, et al. Impaired autophagy in neurons after disinhibition of mammalian target of rapamycin and its contribution to epileptogenesis. J Neurosci. 2012;32:15704-14 pubmed publisher
    ..Thus, our study suggests that impaired autophagy contributes to epileptogenesis, which may be of interest as a potential therapeutic target for epilepsy treatment and/or prevention. ..
  7. Grupp K, Kohl S, Sirma H, Simon R, Steurer S, Becker A, et al. Cysteine-rich secretory protein 3 overexpression is linked to a subset of PTEN-deleted ERG fusion-positive prostate cancers with early biochemical recurrence. Mod Pathol. 2013;26:733-42 pubmed publisher
    ..The tight link of strong CRISP3 expression to the ERG fusion-positive prostate cancers with PTEN deletions provides further evidence for the existence of molecularly distinct subgroups of prostate cancers. ..
  8. Li X, Wang H, Peng X, Zhou H, Wang X. miR-1297 mediates PTEN expression and contributes to cell progression in LSCC. Biochem Biophys Res Commun. 2012;427:254-60 pubmed publisher
    ..Our results document a new epigenetic mechanism for PTEN regulation in LSCC, which is crucial for the development of these tumors. ..
  9. Gerisch G, Schroth Diez B, Müller Taubenberger A, Ecke M. PIP3 waves and PTEN dynamics in the emergence of cell polarity. Biophys J. 2012;103:1170-8 pubmed publisher
    ..Actin clusters were remodeled into a ring along the perimeter of the expanding PIP3 wave. The reverse transition of PIP3 to PTEN was linked to the previous site of wave initiation: where PIP3 decayed first, the entry of PTEN was primed. ..

More Information


  1. McCubrey J, Steelman L, Chappell W, Abrams S, Montalto G, Cervello M, et al. Mutations and deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades which alter therapy response. Oncotarget. 2012;3:954-87 pubmed
    ..This review will first describe these pathways and discuss how genetic mutations and epigenetic alterations can result in resistance to various inhibitors. ..
  2. Sun Z, Zhang L, Hall B, Bian Y, Gutkind J, Kulkarni A. Chemopreventive and chemotherapeutic actions of mTOR inhibitor in genetically defined head and neck squamous cell carcinoma mouse model. Clin Cancer Res. 2012;18:5304-13 pubmed publisher
  3. Miyoshi K, Yanagi S, Kawahara K, Nishio M, Tsubouchi H, Imazu Y, et al. Epithelial Pten controls acute lung injury and fibrosis by regulating alveolar epithelial cell integrity. Am J Respir Crit Care Med. 2013;187:262-75 pubmed publisher
    ..Our results highlight epithelial Pten as a crucial gatekeeper controlling ALI and lung fibrosis by modulating AEC integrity, and the Pten/PI3K/Akt pathway as a potential therapeutic target in these intractable diseases. ..
  4. Kalaitzidis D, Sykes S, Wang Z, Punt N, Tang Y, Ragu C, et al. mTOR complex 1 plays critical roles in hematopoiesis and Pten-loss-evoked leukemogenesis. Cell Stem Cell. 2012;11:429-39 pubmed publisher
    ..These data delineate critical roles for mTORC1 in hematopoietic function and leukemogenesis and inform clinical strategies based on chronic mTORC1 inhibition. ..
  5. Kitagishi Y, Matsuda S. Redox regulation of tumor suppressor PTEN in cancer and aging (Review). Int J Mol Med. 2013;31:511-5 pubmed publisher
    ..In this review, PTEN and the roles of oxidative stress in phosphoinositide-3 kinase/AKT signaling are summarized with a focus on the links between the pathways and ROS in cancer and aging. ..
  6. Chen J, Shao P, Cao Q, Li P, Li J, Cai H, et al. Genetic variations in a PTEN/AKT/mTOR axis and prostate cancer risk in a Chinese population. PLoS ONE. 2012;7:e40817 pubmed publisher
  7. McCubrey J, Steelman L, Chappell W, Abrams S, Franklin R, Montalto G, et al. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascade inhibitors: how mutations can result in therapy resistance and how to overcome resistance. Oncotarget. 2012;3:1068-111 pubmed
  8. Zhang L, Ho Fun Lee V, Wong A, Kwong D, Zhu Y, Dong S, et al. MicroRNA-144 promotes cell proliferation, migration and invasion in nasopharyngeal carcinoma through repression of PTEN. Carcinogenesis. 2013;34:454-63 pubmed publisher
    ..Taken together, we provide compelling evidence that miR-144 functions as an onco-miRNA in NPC, and its oncoeffects are mediated chiefly by repressing PTEN expression to activate the PI3K/Akt pathway. ..
  9. Putz U, Howitt J, Doan A, Goh C, Low L, Silke J, et al. The tumor suppressor PTEN is exported in exosomes and has phosphatase activity in recipient cells. Sci Signal. 2012;5:ra70 pubmed
    ..Thus, we suggest that the ability of PTEN to exert phosphatase activity beyond the cell in which it is produced has implications for PTEN function during development, health, and disease. ..
  10. Yang S, Huang C, Li X, Yu M, He Y, Li J. miR-21 confers cisplatin resistance in gastric cancer cells by regulating PTEN. Toxicology. 2013;306:162-8 pubmed publisher
    ..These results suggest that miR-21 may provide a novel mechanism for understanding cisplatin resistance in gastric cancer by modulating PTEN/PI3K/Akt pathway. ..
  11. Goo C, Lim H, Ho Q, Too H, Clement M, Wong K. PTEN/Akt signaling controls mitochondrial respiratory capacity through 4E-BP1. PLoS ONE. 2012;7:e45806 pubmed publisher
    ..In conclusion, PTEN inactivation bestowed a bioenergetic advantage to the cells by up-regulating mitochondrial respiratory capacity through the 4E-BP1-mediated protein translation pathway. ..
  12. Lumb C, Sansom M. Defining the membrane-associated state of the PTEN tumor suppressor protein. Biophys J. 2013;104:613-21 pubmed publisher
    ..Finally, our simulations suggest that the oncogenicity of the R335L mutation may be due to a reduction in the interaction of the mutant PTEN with anionic lipids. ..
  13. O Roak B, Vives L, Fu W, Egertson J, Stanaway I, Phelps I, et al. Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. Science. 2012;338:1619-22 pubmed publisher
    ..Our data support associations between specific genes and reciprocal subphenotypes (CHD8-macrocephaly and DYRK1A-microcephaly) and replicate the importance of a ?-catenin-chromatin-remodeling network to ASD etiology. ..
  14. Bubien V, Bonnet F, Brouste V, Hoppe S, Barouk Simonet E, David A, et al. High cumulative risks of cancer in patients with PTEN hamartoma tumour syndrome. J Med Genet. 2013;50:255-63 pubmed publisher
    ..New recommendations for the management of PHTS patients are proposed. ..
  15. Napoli E, Ross Inta C, Wong S, Hung C, Fujisawa Y, Sakaguchi D, et al. Mitochondrial dysfunction in Pten haplo-insufficient mice with social deficits and repetitive behavior: interplay between Pten and p53. PLoS ONE. 2012;7:e42504 pubmed publisher
  16. Shan S, Fang L, Shatseva T, Rutnam Z, Yang X, Du W, et al. Mature miR-17-5p and passenger miR-17-3p induce hepatocellular carcinoma by targeting PTEN, GalNT7 and vimentin in different signal pathways. J Cell Sci. 2013;126:1517-30 pubmed publisher
    ..We anticipate that our assay will serve as a helpful model for studying miRNA regulation. ..
  17. Johnsson P, Ackley A, Vidarsdottir L, Lui W, 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 pubmed publisher
    ..Disruption of this asRNA-regulated network induces cell-cycle arrest and sensitizes cells to doxorubicin, which suggests a biological function for the respective PTENpg1 expressed asRNAs. ..
  18. Perez E, Dueck A, McCullough A, Chen B, Geiger X, Jenkins R, et al. Impact of PTEN protein expression on benefit from adjuvant trastuzumab in early-stage human epidermal growth factor receptor 2-positive breast cancer in the North Central Cancer Treatment Group N9831 trial. J Clin Oncol. 2013;31:2115-22 pubmed publisher
  19. Ravi Y, Selvendiran K, Naidu S, Meduru S, Citro L, Bognar B, et al. Pulmonary hypertension secondary to left-heart failure involves peroxynitrite-induced downregulation of PTEN in the lung. Hypertension. 2013;61:593-601 pubmed publisher
    ..In conclusion, peroxynitrite and peroxynitrite-mediated PTEN inactivation seem to be key mediators of lung microvascular remodeling associated with PH secondary to LHF. ..
  20. Pires M, Hopkins B, Saal L, PARSONS R. Alterations of EGFR, p53 and PTEN that mimic changes found in basal-like breast cancer promote transformation of human mammary epithelial cells. Cancer Biol Ther. 2013;14:246-53 pubmed publisher
    ..Consideration should be given to targeting EGFR and restoring p53 and PTEN signaling simultaneously as a strategy for treatment of this subtype of breast cancer. ..
  21. Ittner A, Block H, Reichel C, Varjosalo M, Gehart H, Sumara G, et al. Regulation of PTEN activity by p38?-PKD1 signaling in neutrophils confers inflammatory responses in the lung. J Exp Med. 2012;209:2229-46 pubmed publisher
    ..Thus, aberrant p38?-PKD1 signaling in neutrophils may underlie development of ALI and life-threatening ARDS in humans. ..
  22. Shenoy S, Nanda H, Lösche M. Membrane association of the PTEN tumor suppressor: electrostatic interaction with phosphatidylserine-containing bilayers and regulatory role of the C-terminal tail. J Struct Biol. 2012;180:394-408 pubmed publisher
    ..Arresting the C-terminal tail in this conformation by phosphorylation may provide a control mechanism for PTEN's membrane binding and activity. ..
  23. Cordier F, Chaffotte A, Terrien E, Prehaud C, Theillet F, Delepierre M, et al. Ordered phosphorylation events in two independent cascades of the PTEN C-tail revealed by NMR. J Am Chem Soc. 2012;134:20533-43 pubmed publisher
    ..Besides emphasizing the ability of NMR to quantitatively and dynamically follow post-translational modifications, these results bring a temporal dimension on the establishment of PTEN phosphorylation cascades. ..
  24. Zhang L, Sun Z, Bian Y, Kulkarni A. MicroRNA-135b acts as a tumor promoter by targeting the hypoxia-inducible factor pathway in genetically defined mouse model of head and neck squamous cell carcinoma. Cancer Lett. 2013;331:230-8 pubmed publisher
    ..Thus, our data demonstrate that miR-135b acts as a tumor promoter by promoting cancer cell proliferation, colony formation, survival, and angiogenesis through activation of HIF-1α in HNSCC. ..
  25. Klein S, Sharifi Hannauer P, Martinez Agosto J. Macrocephaly as a clinical indicator of genetic subtypes in autism. Autism Res. 2013;6:51-6 pubmed publisher
    ..The identification of three distinct phenotypic subgroups within macrocephaly autism patients may allow for the identification of their respective distinct genetic etiologies that to date have remained elusive. ..
  26. Veillette A, Grenier K, Brasseur K, Fréchette Frigon G, Leblanc V, Parent S, et al. Regulation of the PI3-K/Akt survival pathway in the rat endometrium. Biol Reprod. 2013;88:79 pubmed publisher
    ..These results suggest that Akt and XIAP may be important surviving signaling molecules by which apoptosis is regulated in the rat endometrium during pregnancy and that TGF-beta could be linked to this process...
  27. Li H, Yang B. Stress response of glioblastoma cells mediated by miR-17-5p targeting PTEN and the passenger strand miR-17-3p targeting MDM2. Oncotarget. 2012;3:1653-68 pubmed
    ..Finally, we demonstrated that miR-17 could repress MDM2 levels, resulting in decreased cell proliferation and drug-resistance. Our results added a new layer of functional mechanism for the well-studied miRNA miR-17. ..
  28. Conde Perez A, Larue L. PTEN and melanomagenesis. Future Oncol. 2012;8:1109-20 pubmed publisher
    ..Moreover, the acquisition of basic knowledge will help patient management with appropriate therapies that are already, or will shortly be, on the market. ..
  29. González Santamaría J, Campagna M, Ortega Molina A, Marcos Villar L, de la Cruz Herrera C, Gonzalez D, et al. Regulation of the tumor suppressor PTEN by SUMO. Cell Death Dis. 2012;3:e393 pubmed publisher
    ..Moreover, we found that virus infection induces PTEN SUMOylation and favors PTEN localization at the cell membrane. Finally, we demonstrated that SUMOylation contributes to the control of virus infection by PTEN. ..
  30. Magee J, Ikenoue T, Nakada D, Lee J, Guan K, Morrison S. Temporal changes in PTEN and mTORC2 regulation of hematopoietic stem cell self-renewal and leukemia suppression. Cell Stem Cell. 2012;11:415-28 pubmed publisher
    ..Developmental changes in key signaling pathways therefore confer temporal changes upon stem cell self-renewal and tumor suppressor mechanisms. ..
  31. Liu Z, Wang H, Liu J, Wang Z. 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 pubmed publisher
    ..Taken together, these results provide evidence to show the promotion role of miR-21 in NSCLC development through modulation of the PTEN signaling pathway. ..
  32. Abe A, Minaguchi T, Ochi H, Onuki M, Okada S, Matsumoto K, et al. PIK3CA overexpression is a possible prognostic factor for favorable survival in ovarian clear cell carcinoma. Hum Pathol. 2013;44:199-207 pubmed publisher
    ..PIK3CA may serve as a biomarker for good prognosis and a possible therapeutic target in this lethal subtype of ovarian cancer. ..
  33. 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 pubmed publisher
  34. Jones N, Bonnet F, Sfar S, Lafitte M, Lafon D, Sierankowski G, et al. Comprehensive analysis of PTEN status in breast carcinomas. Int J Cancer. 2013;133:323-34 pubmed publisher
    ..4 × 10(-13) ) thus may represent a tumor subgroup with a common molecular alteration which could be targeted to improve clinical outcome. ..
  35. Riquelme S, Hopkins B, Wolfe A, Dimango E, Kitur K, Parsons R, et al. Cystic Fibrosis Transmembrane Conductance Regulator Attaches Tumor Suppressor PTEN to the Membrane and Promotes Anti Pseudomonas aeruginosa Immunity. Immunity. 2017;47:1169-1181.e7 pubmed publisher
    ..These findings suggest that improved CFTR trafficking could enhance P. aeruginosa clearance from the CF airway by activating PTEN-mediated anti-bacterial responses and might represent a therapeutic strategy. ..
  36. Norsworthy M, Bei F, Kawaguchi R, Wang Q, Tran N, Li Y, et al. Sox11 Expression Promotes Regeneration of Some Retinal Ganglion Cell Types but Kills Others. Neuron. 2017;94:1112-1120.e4 pubmed publisher
    ..We conclude that Sox11 can reprogram adult RGCs to a growth-competent state, suggesting that different growth-promoting interventions promote regeneration in distinct neuronal types. ..
  37. Zhang X, Huang T, Wu Y, Peng W, Xie H, Pan M, et al. Inhibition of the PI3K-Akt-mTOR signaling pathway in T lymphocytes in patients with active tuberculosis. Int J Infect Dis. 2017;59:110-117 pubmed publisher
    ..tuberculosis can induce FoxP3+Treg cell to expand. ..
  38. Ma L, Wang D, Yu X, Zhou Y. Tangeretin induces cell cycle arrest and apoptosis through upregulation of PTEN expression in glioma cells. Biomed Pharmacother. 2016;81:491-6 pubmed publisher
    ..Hence, the present findings suggest that TANG may be a therapeutic agent for glioblastoma treatment. ..
  39. Kral J, Kuttke M, Schrottmaier W, Birnecker B, Warszawska J, Wernig C, et al. Sustained PI3K Activation exacerbates BLM-induced Lung Fibrosis via activation of pro-inflammatory and pro-fibrotic pathways. Sci Rep. 2016;6:23034 pubmed publisher
    ..This might point to an uncontrolled wound healing response in which the inflammatory as well as tissue repair mechanisms proceed in parallel, thereby preventing resolution and at the same time promoting extensive fibrosis. ..
  40. Li H, Lin S, Huang C, Lu F, Chiu P, Huang W, et al. miR-302 Attenuates Amyloid-β-Induced Neurotoxicity through Activation of Akt Signaling. J Alzheimers Dis. 2016;50:1083-98 pubmed publisher
  41. Krishnan A, Duraikannu A, Zochodne D. Releasing 'brakes' to nerve regeneration: intrinsic molecular targets. Eur J Neurosci. 2016;43:297-308 pubmed publisher
    ..Insights into the roles and importance of these pathways may open new avenues for improving the neurological deficits associated with nerve injury. ..
  42. Gomez Rodriguez J, Wohlfert E, Handon R, Meylan F, Wu J, Anderson S, et al. Itk-mediated integration of T cell receptor and cytokine signaling regulates the balance between Th17 and regulatory T cells. J Exp Med. 2014;211:529-43 pubmed publisher
    ..Our results demonstrate that Itk helps orchestrate positive feedback loops integrating multiple T cell signaling pathways, suggesting Itk as a potential target for altering the balance between Th17 and Treg cells. ..
  43. Graziano A, Parenti R, Avola R, Cardile V. Krabbe disease: involvement of connexin43 in the apoptotic effects of sphingolipid psychosine on mouse oligodendrocyte precursors. Apoptosis. 2016;21:25-35 pubmed publisher
    ..It could open unexplored perspective also for other demyelinating diseases. ..
  44. De La Parra C, Castillo Pichardo L, Cruz Collazo A, Cubano L, Redis R, Calin G, et al. Soy Isoflavone Genistein-Mediated Downregulation of miR-155 Contributes to the Anticancer Effects of Genistein. Nutr Cancer. 2016;68:154-64 pubmed publisher
    ..Therefore, genistein-mediated downregulation of miR-155 contributes to the anticancer effects of genistein in metastatic breast cancer. ..
  45. Chen J, Cai G, Chen X, Liu H, Chen X, Peng Y, et al. Effect of TIMP1 transfection on PTEN expression in human kidney proximal tubular cells. Genet Mol Res. 2015;14:17373-83 pubmed publisher
    ..Our study provides a theoretical basis for further exploration of the mechanism underlying TIMP- 1 participation in renal aging progression. ..
  46. Qu L, Gao Y, Sun H, Wang H, Liu X, Sun D. Role of PTEN-Akt-CREB Signaling Pathway in Nervous System impairment of Rats with Chronic Arsenite Exposure. Biol Trace Elem Res. 2016;170:366-72 pubmed publisher
  47. Castillo Martin M, Thin T, Collazo Lorduy A, Cordon Cardo C. Immunopathologic Assessment of PTEN Expression. Methods Mol Biol. 2016;1388:23-37 pubmed publisher
    ..Importantly, analyses of well-known downstream markers, such as AKT or mTOR, may be used to further analyze PTEN functional status. ..
  48. Salahuddin H, Mansoor Q, Batool R, Farooqi A, Mahmood T, Ismail M. Anticancer activity of Cynodon dactylon and Oxalis corniculata on Hep2 cell line. Cell Mol Biol (Noisy-le-grand). 2016;62:60-3 pubmed
    ..Anticancer activity of these plants on the cancer cell line showed the presence of anticancer components which should be characterized to be used as anticancer therapy. ..
  49. Dudgeon C, Chan C, Kang W, Sun Y, Emerson R, Robins H, et al. The evolution of thymic lymphomas in p53 knockout mice. Genes Dev. 2014;28:2613-20 pubmed publisher
    ..The initial inherited loss of p53 functions appeared to delineate an order of genetic alterations selected for during the evolution of these thymic lymphomas. ..
  50. Shen H, Wang D, Li L, Yang S, Chen X, Zhou S, et al. MiR-222 promotes drug-resistance of breast cancer cells to adriamycin via modulation of PTEN/Akt/FOXO1 pathway. Gene. 2017;596:110-118 pubmed publisher
  51. Xu F, Zhang C, Cui J, Liu J, Li J, Jiang H. The prognostic value and potential drug target of phosphatase and tensin homolog in breast cancer patients: A meta-analysis. Medicine (Baltimore). 2017;96:e8000 pubmed publisher
    ..Our meta-analysis demonstrates that PTEN loss is of particular importance for predicting breast cancer aggressiveness and poor prognosis. PTEN is a potential drug target for the development of individualized treatment in BC patients. ..
  52. Sellitto C, Li L, Gao J, Robinson M, Lin R, Mathias R, et al. AKT activation promotes PTEN hamartoma tumor syndrome-associated cataract development. J Clin Invest. 2013;123:5401-9 pubmed publisher
    ..These findings identify a direct role for PTEN in the regulation of lens ion transport through an AKT-dependent modulation of Na+/K+-ATPase activity, and provide a new animal model to investigate cataract development in PHTS patients. ..
  53. Certal V, Carry J, Halley F, Virone Oddos A, Thompson F, Filoche Rommé B, et al. Discovery and optimization of pyrimidone indoline amide PI3K? inhibitors for the treatment of phosphatase and tensin homologue (PTEN)-deficient cancers. J Med Chem. 2014;57:903-20 pubmed publisher
    ..Following successful development, compound 28 entered phase I/Ib clinical trial in patients with advanced cancer. ..