Knockdown of RAC1 and VASP gene expression inhibits breast cancer cell migration.

Abstract

The ability of tumor cells to migrate is biologically fundamental for tumorigenesis, growth, metastasis and invasion. The present study examined the role of Ras-related C3 botulinum toxin substrate (RAC1) and vasodilator-stimulated phosphoprotein (VASP) in breast cancer cell migration. According to data in Kaplan, Oncomine and The Cancer Genome Atlas, increased expression levels of RAC1 and VASP in breast cancer are associated with decreased cancer cell differentiation, advanced pathological stage and more aggressive tumor subtypes, while increased VASP mRNA expression levels are positively correlated with a poor prognosis in patients with breast cancer. The short hairpin (sh)RNA technique was employed to knock down the expression of RAC1 or VASP. Stable interference with the expression of RAC1 or VASP using RAC1-shRNA or VASP-shRNA, respectively, was established in MCF-7 breast cancer cells. In RAC1-shRNA or VASP-shRNA cells, the protein expression levels of RAC1 or VASP were significantly downregulated compared with control cells. The proliferation and migration rates of the RAC1-shRNA or VASP-shRNA cells were significantly lower compared with control cells. It was observed that the protein expression levels of VASP also decreased in RAC1-shRNA cells compared with control cells. The results revealed that RAC1 and VASP may serve important roles in promoting the migration of MCF-7 breast cancer cells, and that VASP may among the downstream signaling molecules associated with RAC1.