Objective To investigate the role of activin A, a member of transforming growth factor-β superfamily cytokine, in regulating migration and aerobic glycolysis of gastric cancer cells, and the prognostic value of the expression of its coding gene inhibin βA(INHBA) in survival of gastric cancer patients. Methods The gastric cells were first titrated with various concentration of activin A and the expression of pSmad2/3 was examined by Western blot(WB) to determine the concentration range of activin A used in the study. The effect of activin A on the migration of gastric cancer cells was monitored by transwell and wound healing assays. The lactate production and glucose uptake of gastric cancer cells were followed to evaluate the role of activin A on the regulation of aerobic glycolysis. The association between activin A and epithelial mesenchymal transformation(EMT)/glycolysis related genes was analyzed in the Cancer Genome Atlas (TCGA) gastric cancer database, and further validated by WB studies. The expression of INHBA in gastric cancer and normal mucosa tissue were analyzed in TCGA, Gene Expression Omnibus(GEO) and other publicly available databases to explore the association of INHBA expression level with patients’ survival. Results The activin A at 20 ng/mL sufficiently upregulate the level of pSmad2/3, and the concentration was thus used in the study. Activin A promoted migration and aerobic glycolysis of gastric cancer cells. There was a significant positive correlation between the expression of INHBA and several EMT related genes, hypoxia inducible factor-1 α(HIF1A), glucose transporter 3 (GLUT3) [SNAI1: r=0.47, P=0;SNAI2: r=0.51, P=0; VIM: r=0.37, P=2.1×10-14; matrix metalloproteinase(MMP)2: r=0.64, P=0; MMP9: r=0.27, P=2.8×10-8; HIF1A: r=0.45, P=0; SLC2A3: r=0.42, P=0]. After treatment with activin A, the expression of snail, slug, vimentin, MMP2 and GLUT3 increased significantly(P<0.05). The expression of INHBA in gastric cancer was significantly higher than that in normal gastric mucosa tissue, and the prognosis of patients with higher expression of INHBA was poor. Conclusions Activin A can promote migration and aerobic glycolysis, which might attribute to its upregulation of EMT related genes and GLUT3. High level of INHBA is indicative of prognosis for gastric cancer patients.
