Grb2-associated binder 2 silencing impairs growth and migration of H1975 cells via modulation of PI3K-Akt signaling.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death and often has a poor prognosis. Investigation of NSCLC cancer cell migration, invasion and development of strategies to block this process is essential to improve the disease prognosis. In this study, we tested our hypothesis that Grb2-associated binder 2 (Gab2) regulate NSCLC cancer cell H1975 malignant biological behaviors, and silencing Gab2 reduced H1975 cellular colony forming ability, migration and invasion. Moreover, silenced cells present defects in phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (Akt) signaling, and reduced expression/activity of matrix metallopeptidase (MMP)-2/9. Furthermore, in Gab2 siRNA-transfected cells, we detected a decrease in signal transducer and activator of transcription 3 (STAT3) phosphorylation and nuclear translocation. In vivo, Gab2 siRNA cells inoculated subcutaneously in nude mice demonstrated decreased tumor growth and PI3K-Akt signaling inhibition. These results indicate that Gab2 is a key factor in H1975 tumor migration, invasion, suggesting that Gab2 can be a novel therapeutic target in NSCLC.