Both lipid- and protein-phosphatase activities of PTEN contribute to the p53-PTEN anti-invasion pathway

• Published in: Cell cycle (Georgetown, Tex.) Tex.), 2010-11, Vol.9 (22), p.4450-4454
• Main Authors: Poon, Jacquelyne S., Eves, Robert, Mak, Alan S.
• Format: Article
• Language: English
• Subjects: Animals; Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cell Movement; Cycle; Landes; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - metabolism; Neoplasms - metabolism; Organogenesis; Phosphatidylinositol 3-Kinases - metabolism; Proteins; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; PTEN Phosphohydrolase - physiology; Rats; RNA Interference; RNA, Small Interfering; Signal Transduction; src-Family Kinases - metabolism; STAT3 Transcription Factor - metabolism; Tumor Suppressor Protein p53 - metabolism; Up-Regulation
• ISSN: 1538-4101; 1551-4005
• DOI: 10.4161/cc.9.22.13936

We have recently identified mutually antagonizing signaling pathways that regulate podosome formation and invasive phenotypes in Src-transformed vascular smooth muscle cells and fibroblasts. Cross-talks between the anti-invasion p53-PTEN, and the pro-invasion Src-Stat3 and Src-PI3K-Akt pathways serve as a check and balance that dictates the outcome of either an invasive or non-invasive phenotype. Using a retrovirus vector encoding PTEN phosphatase mutants that retain either protein- or lipid-phosphatase activity on a Src(Y527F)background, we report here that both lipid- and protein-phosphatase activities of PTEN contribute to the suppression of Src-induced podosome formation and associated invasive phenotypes in rat aortic smooth muscle cells. This data suggests that p53 up-regulation of PTEN inhibits cell invasion via a two-prong mechanism: inactivating podosome agonists by its protein-phosphatase activity on the one hand, and antagonising the PI3K-Akt pathway by its lipid-phosphatase activity on the other.