title: The lipid phosphatase activity of PTEN is critical for stabilizing intercellular junctions and reverting invasiveness.
abstract: To analyze the implication of PTEN in the control of tumor cell invasiveness, the canine kidney epithelial cell lines MDCKras-f and MDCKts-src, expressing activated Ras and a temperature-sensitive v-Src tyrosine kinase, respectively, were transfected with PTEN expression vectors. Likewise, the human PTEN-defective glioblastoma cell lines U87MG and U373MG, the melanoma cell line FM-45, and the prostate carcinoma cell line PC-3 were transfected. We demonstrate that ectopic expression of wild-type PTEN in MDCKts-src cells, but not expression of PTEN mutants deficient in either the lipid or both the lipid and protein phosphatase activities, reverted the morphological transformation, induced cell-cell aggregation, and suppressed the invasive phenotype in an E-cadherin-dependent manner. In contrast, overexpression of wild-type PTEN did not counteract Ras-induced invasiveness of MDCKras-f cells expressing low levels of E-cadherin. PTEN effects were not associated with marked changes in accumulation or phosphorylation levels of E-cadherin and associated catenins. Wild-type, but not mutant, PTEN also reverted the invasive phenotype of U87MG, U373MG, PC-3, and FM-45 cells. Interestingly, PTEN effects were mimicked by N-cadherin-neutralizing antibody in the glioblastoma cell lines. Our data confirm the differential activities of E- and N-cadherin on invasiveness and suggest that the lipid phosphatase activity of PTEN exerts a critical role in stabilizing junctional complexes and restraining invasiveness.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U410, Faculté de Médecine Bichat, 75018 Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Kotelevets
authors.forename: J
authors.initials: J
authors.lastname: van Hengel
authors.forename: E
authors.initials: E
authors.lastname: Bruyneel
authors.forename: M
authors.initials: M
authors.lastname: Mareel
authors.forename: F
authors.initials: F
authors.lastname: van Roy
authors.forename: E
authors.initials: E
authors.lastname: Chastre
mesh_terms: D000818:Animals; D002460:Cell Line; D005909:Glioblastoma / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology*; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000503:physiopathology*; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000502:physiology; D011471:Prostatic Neoplasms / Q000473:pathology / Q000503:physiopathology*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000502:physiology
chemical_list: D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human