Membrane-bound beta-catenin degradation is enhanced by ETS2-mediated Siah1 induction in Helicobacter pylori-infected gastric cancer cells

作者：Das L; Kokate S B; Dixit P; Rath S; Rout N; Singh S P; Crowe S E; Bhattacharyya A

来源：Oncogenesis, 2017, 6(5): e327.

DOI：10.1038/oncsis.2017.26

beta-catenin has two different cellular functions: intercellular adhesion and transcriptional activity. The E3 ubiquitin ligase Siah1 causes ubiquitin-mediated degradation of the cytosolic beta-catenin and therefore, impairs nuclear translocation and oncogenic function of beta-catenin. However, the effect of Siah1 on the cell membrane bound beta-catenin has not been studied. In this study, we identified that the carcinogenic bacterium H. pylori increased ETS2 transcription factor-mediated Siah1 protein expression in gastric cancer cells (GCCs) MKN45, AGS and Kato III. Siah1 protein level was also noticeably higher in gastric adenocarcinoma biopsy samples as compared to non-cancerous gastric epithelia. Siah1 knockdown significantly decreased invasiveness and migration of H. pylori-infected GCCs. Although, Siah1 could not increase degradation of the cytosolic beta-catenin and its nuclear translocation, it enhanced degradation of the membrane-bound beta-catenin in the infected GCCs. This loss of membrane-bound pool of beta-catenin was not associated with the proteasomal degradation of E-cadherin. Thus, this work delineated the role of Siah1 in increasing invasiveness of H. pylori-infected GCCs.

• 出版日期2017-5