Role of c-Src and c-Abl in breast cancer cell migration and metastasis

Introduction: The HEr2 receptor member of the epidermal growth factor (EGF) receptor family are overexpressed in 25% of human breast cancers conferring a more aggressive biology. Similarly c-Src is overexpressed in solid tumors like breast cancer, in correlation with ErbB2, suggesting it plays a role in downstream receptor signaling and cellular migration. Previous studies have suggested that c-Abl is activated downstream HEr2 receptor in breast cancer cells cell migration. We hypothesize that c-Src and c-Abl are activated downstream HEr2 signaling and increasing migration activity in human breast cancer cells. Material and methods: The effects of EGF stimuli and kinases inhibitors were evaluated using assay to measure migration. Western blotting was used to monitor its effects on cell signaling. Results: Our results suggests that c-Src is activated downstream signaling of HEr2 before activation of c- Abl, increasing cellular migration, through a different signaling pathway than AKT and MAPKS and its downstream targets. Discussion: Our study describes a new signaling pathway downstream HEr2 receptor where c-Src and c-Abl are implicated and have a key role on migration for breast cancer cells. These data suggest that inhibitors targeted against c-Src or c-Abl kinases could potentially be useful in preventing breast cancer progression.