Junqi He
Capital Medical University, China
Title: PDZK1 targets PTEN to inhibits AKT signaling and malignant phenotypes in gastric
Biography
Biography: Junqi He
Abstract
PI3K/AKT pathway, which is frequently altered in gastric carcinoma, can be negatively regulated via dephosphorylation of PIP3 to PIP2 by PTEN. In the present study, PDZK1 was identified as a novel binding protein of PTEN, in which the interaction was mediated by the PDZ2 and PDZ3 domain of PDZK1 with the last four amino acids (ITKV) in the carboxyl terminus of PTEN (PTEN-CT). Our data from PDZK1 overexpression and siRNA-mediated knockdown experiments further demonstrated that by associating with PTEN, PDZK1 inhibits the phosphorylation of PTEN. In addition, overexpression of PDZK1 down-regulated AKT and ERK signals. Consistent with these results, PDZK1 suppressed gastric cancer cell proliferation, impeded the formation of anchorage independent colonies in soft agar and retarded the growth of xenografts in nude mice. Furthermore, PDZK1 was significantly downregulated in gastric cancer tissues in comparison to that in normal gastric tissues. Collectively, this study shows that downregulation of PDZK1 expression enhances the PTEN inactivation, which may contribute to the carcinogenesis of gastric cancer.