Rab11a Is Overexpressed in Gastric Cancer and Regulates FAK/AKT Signaling.

Abstract

Dysregulation of Rab11a has been implicated in the progression of several cancers. However, there have been no such studies for human gastric cancers. In the current study, we examined Rab11a protein expression and found it was upregulated in 49 of 108 gastric cancer tissues and correlated with local invasion, nodal metastasis, and advanced stage. Rab11a protein was higher in gastric cancer cell lines than normal gastric cell line. We transfected Rab11a plasmid and siRNA in both MGC803 and AGS cell lines. Rab11a overexpression increased the cell growth rate, colony numbers, and invasion ability in both MGC803 and AGS cell lines. Downregulation of Rab11a using siRNA decreased the cell proliferation rate, colony numbers, and inhibited invasion. Rab11a overexpression also conferred cisplatin resistance. Annexin V/PI staining showed that Rab11a overexpression suppressed cisplatin-induced apoptosis, while Rab11a depletion promoted cell apoptosis. We also showed that Rab11a overexpression maintained mitochondrial membrane potential. Western blot analysis revealed that Rab11a increased protein expression of MMP2, cyclin D1, Bcl-2, p-FAK, and p-AKT, while Rab11a depletion showed the opposite effects. Blockage of FAK using inhibitor downregulated Bcl-2, cyclin D1, MMP2, and p-AKT expression and abolished the effects of Rab11a on these proteins. In summary, our data demonstrated that Rab11a is upregulated in human gastric cancers. Rab11a facilitated cell proliferation and invasion, as well as cisplatin sensitivity and mitochondrial membrane potential, possibly via the FAK/AKT signaling pathway.

• Authors: Jiang Du, Lin Fu, Jie Hao, Xiumin Lin, Qianze Dong
• Journal: Journal of oncology (J Oncol) Vol. 2020 Pg. 3494396 ( 2020) ISSN: 1687-8450 [Print] Egypt
• PMID: 33178272 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Jiang Du et al.