ARHGEF10L expression regulates cell proliferation and migration in gastric tumorigenesis

• Published in: Bioscience, biotechnology, and biochemistry Vol. 84; no. 7; pp. 1362 - 1372
• Main Authors: Wang, Da-wei, Tang, Jun-yi, Zhang, Guo-qing, Chang, Xiao-tian
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02.07.2020; Oxford University Press
• Subjects: ARHGEF10L; Carcinogenesis - genetics; Carcinogenesis - metabolism; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Cytoskeletal Proteins - metabolism; EMT; Epithelial-Mesenchymal Transition - genetics; gastric cancer; HSP70 Heat-Shock Proteins - metabolism; Humans; Membrane Proteins - metabolism; Microfilament Proteins - metabolism; Prognosis; proliferation; Rho Guanine Nucleotide Exchange Factors - genetics; Rho Guanine Nucleotide Exchange Factors - metabolism; rho-Associated Kinases - metabolism; RhoA; rhoA GTP-Binding Protein - metabolism; Signal Transduction - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Transfection; ARHGEF10L; gastric cancer; proliferation; EMT; RhoA
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1080/09168451.2020.1737503

We recently reported that Rho guanine nucleotide exchange factor 10-like protein (ARHGEF10L) activated Rho GTPases as guanine nucleotide exchange factor to stimulate liver tumorigenesis. The present study continued to explore the effect of ARHGEF10L on the tumorigenic process of gastric cancer. This study detected increased expression of ARHGEF10L in GC tissues compared to peritumoral tissue samples. SGC7901 cells with ARHGEF10L overexpression showed increased cell proliferation, cell migration, and tube-like structure formation abilities, as well as increased expression of GTP-RhoA, ROCK1, and phospho-Ezrin/Radixin/Moesin. ARHGEF10L overexpression downregulated the expression of E-cadherin and upregulated the expression of N-cadherin and Slug, indicating an activation of EMT in the transfected cells. RNA-sequencing assay detected an increased expression of Heat shock 70 kDa protein 6 in the SGC7901 cells overexpressing ARHGEF10L. The above results suggest that ARHGEF10L expression can stimulate gastric tumorigenesis by prompting RhoA-ROCK1-phospho-ERM signaling, inducing EMT and increasing HSPA6 expression. High expression of ARHGEF10L in gastric tumor stimulated tumor cell proliferation and migration by activating GTP-RhoA-ROCK1-phospho-ERM signaling and inducing EMT. ARHGEF10L: rho guanine nucleotide exchange factor 10-Like1; ERM: Ezrin/Radixin/Moesin; EMT: epithelial-mesenchymal transition; GC: gastric cancer; HSPA6: Heat shock 70 kDa protein 6; RhoA: Ras homolog gene family member A; RhoGEFs: Rho family guanine nucleotide exchange factors; ROCK1: Rho-associated coiled-coil kinase-1