Knockdown of Gab1 Inhibits Cellular Proliferation, Migration, and Invasion in Human Oral Squamous Carcinoma Cells

Abstract

Grb2-associated binder 1 (Gab1) is often aberrant in cancerous cells and tissues, whose alteration is responsible for aggressive phenotypes. In this study, we examined the Gab1 expression in human oral squamous cell carcinoma (OSCC) tissues and investigated the cellular and molecular effect of Gab1 on migration, invasion, and cell growth of the OSCC cell lines SCC15 and SCC25. We found that Gab1 was overexpressed in OSCC tissues and cells, which is related to the protein levels of various molecules associated with cellular proliferation, migration, and invasion. Functional assays identified that Gab1 overexpression promoted cell proliferation and invasion of OSCC cells and inhibited cell apoptosis in the SCC15 and SCC25 cell lines. On the other hand, Gab1 silencing affected the proliferation and invasion of OSCC cells and induced cell apoptosis. Western blot assay identified that Gab1 overexpression suppressed the expression of Cdc20 homolog 1 (Cdh1) and then promoted cell invasion in OSCC cells. Furthermore, Gab1-mediated Cdh1 downregulation was significantly reversed when the cells were subjected to an inhibitor of p-Akt. In conclusion, these results suggested that Gab1 induced malignant progression of OSCC cells probably via activation of the Akt/Cdh1 signaling pathway. Thus, Gab1 may be a potential therapeutic target in the treatment of OSCC patients.