C-Src-mediated RANKL-induced breast cancer cell migration by activation of the ERK and Akt pathway

Abstract

The receptor activator for nuclear factor κB ligand/receptor activator for nuclear factor κB (RANKL/RANK) pathway is critical for RANK-expressing cancer cells to home to bones, and c-Src is critical for cancer progression. The objective of this study was to explore the effect of c-Src in the RANKL/RANK pathway and migration activity in human breast cancer cells. Breast cancer cell lines MCF-7, MDA-MB-231 and BT-474 were obtained and cultured. Flow cytometry was used to examine RANK expression. The results showed that RANK was expressed in breast cancer cell lines MCF-7, MDA-MB-231 and BT-474, and soluble RANKL (sRANKL)-triggered migration of breast cancer cells by activating ERK1/2, Akt and c-Src. The sRANKL-induced migration was blocked with RANKL inhibitor osteoprotegerin (OPG), MEK inhibitor PD98059, PI3K inhibitor LY294002 and Src inhibitor PP2. Inhibition of c-Src function with PP2 blocked the activation of Akt and ERK1/2, resulting in the inhibition of RANKL-induced migration. In conclusion, RANKL was found to increase the migration of breast cancer cells by activating the c-Src-Akt and c-Src-ERK signaling pathways.