ISSN: 2161-069X
Journal of Gastrointestinal & Digestive System
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PDZK1 targets PTEN to inhibit AKT signaling and malignant phenotypes in gastric cancer
7th Global Congress on Gastroenterology & Endoscopy
Junqi He, Longyan Yang, Tao Tao, Qiong Qin, Junfang Zheng, Ran Meng, Qiqi Wang, Hua Liu, Ran Song and Ying Xiong
Capital Medical University, Beijing, China
Posters & Accepted Abstracts: J Gastrointest Dig Syst
DOI:
Abstract
PI3K/AKT pathway, which is frequently altered in gastric carcinoma, can be negatively regulated via dephosphorylation of PIP3 to PIP2 by (Phosphatase and Tensin Homolog) 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 over-expression and siRNA-mediated knock-down experiments further demonstrated that by associating with PTEN, PDZK1 inhibits the phosphorylation of PTEN. In addition, over-expression 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 down-regulation of PDZK1 expression enhances the PTEN inactivation, which may contribute to the carcinogenesis of gastric cancer.Biography
Email: jq_he@ccmu.edu.cn
