Breast cancer metastasis suppressor 1 inhibits SDF-1alpha-induced migration of non-small cell lung cancer by decreasing CXCR4 expression.

This report shows that over-expression of BRMS1 reduces SDF-induced chemotaxis and suppresses nuclear factor-kappaB (NF-kappaB) activity in NSCLC cell line. Inhibition of NF-kappaB activity impairs SDF-1alpha-dependent migration and NF-kappaB can directly bind to the chemokine (C-X-C motif) receptor 4 (CXCR4) promoter invivo. However, knockdown of BRMS1 promotes NSCLC cell migration and CXCR4 expression. Furthermore, BRMS1 and CXCR4 expression levels are inversely correlated in the NSCLC cases. The level of BRMS1 mRNA is found to be markedly lower in the distant metastasis group than in the non-distant metastasis group (P=0.003). However, CXCR4 mRNA was higher in the distant metastasis group than in the non-distant metastasis group (P=0.032). These results indicate that BRMS1 regulates metastatic potential at least in part through the down-regulation of CXCR4, to be indirectly regulated by BRMS1 through nuclear factor-kappaB activation.