Rab22a promotes the proliferation, migration, and invasion of lung adenocarcinoma via up-regulating PI3K/Akt/mTOR signaling pathway.

Rab22a, a member of the proto-oncogene RAS family, belongs to the Rab5 subfamily. It participates in early endosome formation and regulates vesicle trafficking. The relationship between Rab22a and tumorigenesis remains elusive. In non-small cell lung cancer specimens, immunohistochemical staining showed consistently high expression of Rab22a in lung adenocarcinoma, but not in squamous cell carcinoma. In lung adenocarcinoma cell lines, A549 and H1299, transfection with Rab22a significantly promoted cell proliferation, migration, and invasion, whereas interference with Rab22a specific siRNA significantly inhibited the above capacities. Transfection with Rab22a also up-regulated the phosphorylation levels of core effector proteins on the PI3K/Akt/mTOR pathway. The Co-IP assay further confirmed the interaction between Rab22a and PI3Kp85α, the core regulatory subunit of PI3K. Application of rapamycin, the mTOR inhibitor, significantly reduced the upregulation of the proliferation, migration, and invasion abilities of lung adenocarcinoma cells transfected with Rab22a. These results suggest that Rab22a can promote the malignant phenotype of lung adenocarcinoma by upregulating the PI3K/Akt/mTOR signaling pathway, and may function as a potential anti-tumor therapeutic target.