Mechanism of GPER promoting proliferation, migration and invasion of triple-negative breast cancer cells through CAF.

Triple-negative breast cancer (TNBC) is an important histological subtype of breast cancer. Abnormal GPER expression has been reported in human breast cancer. However, the functional mechanism of GPER through carcinoma-associated fibroblast (CAF) in TNBC needed further investigations. The proliferation and cycle progression of the MDA-MB-231 cells were respectively analyzed by CCK-8 assay and flow cytometry, while cell migration and invasion were examined by wound healing assay and transwell assay. GPER expression in TNBC tissues and MDA-MB-231 cells was investigated by RT-qPCR, western blotting and immunohistochemistry. Collagen-1 was measured using ELISA. In addition, the role of GPER through CAF was investigated through cells were transfected with GPER interference plasmid and treated with GPER agonist, respectively. The transfection effects were verified by RT-qPCR. The results demonstrated that CAF could promote proliferation, migration and invasion of MDA-MB-231 cells compared with normal fibroblast (NF). GPER expression was decreased in TNBC tissues and MDA-MB-231 cells in comparison with the adjacent normal tissues and MCF-10A cells. GPER expression could affect the expression of Coll-1 in CAF. Downregulation of GPER inhibited Coll-1 expression in CAF, thereby inducing the decrease of cell proliferation, arrest of S phase and suppression of migration and invasion of MDA-MB-231 cells, while GPER agonist could be resulted in the opposite effects. In conclusion, the present data demonstrated that GPER promoted proliferation, migration and invasion of TNBC cells through CAF. Furthermore, GPER expression was positively related to the prognosis of TNBC.