ELK3 Controls Gastric Cancer Cell Migration and Invasion by Regulating ECM Remodeling-Related Genes

Abstract

Current therapeutic strategies for gastric cancer, including surgery and chemotherapy improve patient survival; however, the survival rate of patients with metastatic gastric cancer is very low. The molecular mechanisms underlying the dissemination of gastric cancer cells to distant organs are currently unknown. Here, we demonstrate that the E26 transformation-specific (ETS) transcription factor ELK3 (ELK3) gene is required for the migration and invasion of gastric cancer cells. The ELK3 gene modulates the expression of extracellular matrix (ECM) remodeling-related genes, such as bone morphogenetic protein (BMP1), lysyl oxidase like 2 (LOXL2), Snail family transcriptional repressor 1 (SNAI1), serpin family F member 1 (SERPINF1), decorin (DCN), and nidogen 1 (NID1) to facilitate cancer cell dissemination. Our in silico analyses indicated that ELK3 expression was positively associated with these ECM remodeling-related genes in gastric cancer cells and patient samples. The high expressions of ELK3 and other ECM remodeling-related genes were also closely associated with a worse prognosis of patients with gastric cancer. Collectively, these findings suggest that ELK3 acts as an important regulator of gastric cancer cell dissemination by regulating ECM remodeling.