The Lipid Phosphatase Activity of PTEN Is Critical for Stabilizing Intercellular Junctions and Reverting Invasiveness

• Published in: The Journal of cell biology 2001-12, Vol.155 (7), p.1129-1135
• Main Authors: Kotelevets, Larissa, van Hengel, Jolanda, Bruyneel, Erik, Mareel, Marc, van Roy, Frans, Chastre, Eric
• Format: Article
• Language: English
• Subjects: Aggregation; Animals; Antibodies; Cadherins; Cell Line; Cell lines; Cellular biology; Epithelial cells; Glioblastoma - pathology; Glioblastoma - physiopathology; Humans; Intercellular Junctions - physiology; Kidneys; Lipids; Male; Melanoma - pathology; Melanoma - physiopathology; Neoplasm Invasiveness; Phenotypes; Phosphatases; Phosphoric Monoester Hydrolases - genetics; Phosphoric Monoester Hydrolases - physiology; Prostatic Neoplasms - pathology; Prostatic Neoplasms - physiopathology; PTEN Phosphohydrolase; Recombinant Proteins - metabolism; Transfection; Tumor cell line; Tumor Cells, Cultured; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - physiology; Tumors
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200105109

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.