Knocking down FAM83B inhibits endometrial cancer cell proliferation and metastasis by silencing the PI3K/AKT/mTOR pathway

Abstract

Family with sequence similarity 83 member B (FAM83B) has been recently identified as an oncogene involved in the development of various human cancers. However, the role of FAM83B in endometrial cancer tumorigenesis and metastasis is unclear. In this study, we found that the expression of FAM83B was upregulated in endometrial cancer tissues and cell lines. FAM83B expression in endometrial cancer tissues was significantly higher than that in normal tissues and higher FAM83B expression was closely related to poorly survival rate according to TCGA analysis. Moreover, FAM83B expression was correlated with International Federation of Gynecology and Obstetrics (FIGO)stage and myometrial invasion but had no significant correlation with age or histological grade. FAM83B knockdown inhibited endometrial cancer cell proliferation, migration, and invasion arrested the cell cycle at the G1/S stage and promoted apoptosis. FAM83B knockdown also inhibited endometrial cancer growth and lung metastasis in vivo. FAM83B knockdown silenced the PI3K/AKT/mTOR pathway and promoted autophagy. Furthermore, activation of the PI3K/AKT/mTOR pathway reversed FAM83B knockdown-induced autophagy promotion and inhibition of proliferation, migration, and invasion in endometrial cancer cells. Taken together, these results indicate that FAM83B promotes endometrial cancer cell proliferation and metastasis by inhibiting autophagy via activating the PI3K/AKT/mTOR pathway.

Keywords: Autophagy; Endometrial cancer; FAM83B; Neoplasm Metastasis; PI3K/Akt signalling.