CCL2 induces epithelial-mesenchyme transition in breast cancer MCF-7 cells

Objective To explore the effect and molecular mechanism of CC chemokine ligand 2 (CCL2) on epithelial-mesenchymal transition in human breast cancer cells. Methods Breast cancer Michigan cancer foundation-7 (MCF-7) cells were treated with 50 ng/ml CCL2. The abilities of invasion were detected by Transwell assay. The expression of epithelial-mesenchymal transition (EMT)-associated markers, E-cadherin and vimentin were detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). The expressions of Snail, protein kinase B (AKT), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β) and GSK3β were detected by Western blot. Snail nuclear localization was detected by immunoflurescence staining. Results We found that CCL2 treatment could induce morphological alteration of MCF-7 cells from epithelial morphology to mesenchymal morphology. CCL2 significantly increased the migration of MCF-7 cells, and increased the expression of mesenchymal maker vimentin and decreased epithelial marker E-cadherin. More important, treatment of CCL2 significantly increased the expression of Snail, and promoted the nuclear localization of Snail. Knockdown of Snail significantly reverse the effects of CCL2 on the EMT in MCF-7 cells. Moreover, treatment of CCL2 significantly increased the phosphorylation levels of p-AKT and p-GSK3β, and AKT inhibitor LY294002 significantly inhibited CCL2-induced Snail and p-GSK3β expression. Conclusion CCL2 might induce EMT in MCF-7 cells, by which mechanism is related to activate AKT/GSK3β Snail pathway. Key words: Chemokine CCL2; Breast neoplasms; Tumor cells, cultured; Biotransformation