Non-tumor tissue derived interleukin-17B activates IL-17RB/AKT/β-catenin pathway to enhance the stemness of gastric cancer

Inflammation is a critical component involved in tumor progression. Interleukin-17 (IL-17) belongs to a relatively new family of cytokines that has been associated with the progression of cancers. However, the role of IL-17B/IL-17RB (IL-17 receptor B) signaling to stemness of gastric cancer remains unknown. Here, we confirmed that the expression of IL-17RB in gastric cancer tissues was significantly increased, that overexpression was associated with poor prognosis of gastric cancer patients, and that overexpression was positively correlated with some stemness markers. Interestingly, the expression of IL-17B was upregulated in patient serum rather than gastric tumor tissues. Furthermore, exogenous rIL17B significantly promoted the stemness of gastric cancer cells depending on IL-17RB and induced the expression of IL-17RB. Simultaneously, the expression of phosphorylated AKT, GSK-3 beta, and beta-catenin as well as the nuclear translocation of beta-catenin were significantly increased in the MGC-803 cell in a dose-dependent manner, when treated with rIL-17B. The AKT inhibitor, LY294002, and the knockdown of AKT expression reversed the rIL-17B-induced upregulation of beta-catenin and some stemness markers. Together, our results indicate that the IL-17B/IL-17RB signal can promote the growth and migration of tumor cells, and upregulate cell stemness through activating the AKT/beta-catenin pathway in gastric cancer, suggesting that IL-17RB may be a novel target in human gastric cancer therapy.