FAM49B mediates tumor progression and poor prognosis of gastric cancer through activating PI3K/AKT pathway.

Gastric cancer is a common malignancy worldwide. It has been shown that the actin cytoskeleton modulator family with sequence similarity 49 member B (FAM49B) is involved in the initiation and spread of malignancies. However, the role of FAM49B is still unknown in gastric cancer. We examined FAM49B expression in gastric cancer and its relationship between the clinical pathological features of gastric cancer patients. Lentiviruses packaged sh-FAM49B were transfected into AGS cells, and the FAM49B overexpression plasmids were transfected into HGC-27 cells to perform loss- or gain-of-function assays. Additionally, AGS cells expressing sh-FAM49B were subcutaneously injected into nude mice. In vitro and in vivo experiments were conducted to investigate the role and mechanism of FAM49B in the progresses of gastric cancer. FAM49B was upregulated in gastric cancer that indicated a poor prognosis of gastric cancer patients. FAM49B enhanced cell viability, the percent of EdU positive cells, invaded cell numbers, the relative protein expression level of PD-L1 and the IL-10 concentration, while reduced the percent of CD8 + T cells and the concentration of IFN-γ in vitro. In tumor-bearing mice, knockdown of FAM49B reduced tumor size and weight, and the protein levels of PD-L1 and IFN-γ. FAM49B promoted the expressions of the PI3K/AKT/mTOR axis in vitro and in vivo. Inhibitory role of the FAM49B knockdown in the above-mentioned progresses was reversed with the treatment of 740Y-P. Therefore, FAM49B promoted the gastric cancer cell growth, invasion and immune escape through the PI3K/AKT/mTOR axis.