Depletion of ELMOD3 inhibits the growth and migration of gastric cancer cells by disrupting the β-catenin signaling and the F-actin cytoskeleton

Abstract

ELMOD3 (encoding ELMO domain containing 3) is a causative gene associated with human autosomal dominant nonsyndromic and progressive hearing loss. However, the role of ELMOD3 in the occurrence and development of tumors remains unknown. Herein, we observed that inactivation of ELMOD3 in gastric cancer cells significantly inhibited their proliferation, migration, and invasion, and altered cell cycle progression. A xenograft tumor model showed that knockout of ELMOD3 suppressed the tumorigenicity of BGC823 gastric cancer cells in nude mice. Further investigation demonstrated that the ELMO domain of ELMOD3 interacts with β-catenin, which increases the levels of β-catenin, promoting downstream target gene expression. Deletion of ELMOD3 in gastric cells decreased the β-catenin signaling, elevated E-cadherin levels, suppressed RAF/MEK/ERK signal pathway, and disrupted the formation of F-actin cytoskeleton. These results led us to propose that ELMOD3 may participate in multiple biological processes in promoting the tumorigenesis of gastric cancer. It exerts a positive role in the regulation of gastric cancer cell proliferation and progression. Thus, ELMOD3 was identified as a potential tumor target, which deserves further investigation.