ENKUR recruits FBXW7 to ubiquitinate and degrade MYH9 and further suppress MYH9-induced deubiquitination of β-catenin to block gastric cancer metastasis.

ABSTRACT: ENKUR was shown as a suppressor in some tumors. However, the biological role of ENKUR on gastric cancer (GC) and its related molecular mechanisms is not clear. Here, we first observed that ENKUR significantly inhibited cell migration, invasion, and metastasis in GC. The molecular basis showed β-catenin-mediated epithelial-mesenchymal transition (EMT) signaling was inactivated in ENKUR-overexpressing GC cells. In addition, ENKUR knockdown markedly restored cell migration and invasion. Subsequently, ENKUR bound to MYH9 and decreased its protein expression by recruiting E3 ubiquitin ligase FBXW7 to form an ubiquitinated degradation complex. The downregulated MYH9 protein weakened the recruitment of the deubiquitinase USP2 and thus promoted the degradation of β-catenin protein, which finally s

SUBMITTER: Liu J 

PROVIDER: S-EPMC9697592 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature