CXCL1 stimulates migration and invasion in ER‑negative breast cancer cells via activation of the ERK/MMP2/9 signaling axis

: Chemokine (C‑X‑C motif) ligand 1 (CXCL1), a member of the CXC chemokine family, has been reported to be a critical factor in inflammatory diseases and tumor progression; however, its functions and molecular mechanisms in estrogen receptor α (ER)‑negative breast cancer (BC) remain largely unknown. The present study demonstrated that CXCL1 was upregulated in ER‑negative BC tissues and cell lines compared with ER‑positive tissues and cell lines. Treatment with recombinant human CXCL1 protein promoted ER‑negative BC cell migration and invasion in a dose‑dependent manner, and stimulated the activation of phosphorylated (p)‑ extracellular signal‑regulated kinase (ERK)1/2, but not p‑STAT3 or p‑AKT. Conversely, knockdown of CXCL1 in BC cells attenuated these effects. Additionally, CXCL1 increased the expression of matrix metalloproteinase (MMP)2/9 via the ERK1/2 pathway. Inhibition of MEK1/2 by its antagonist U0126 reversed the effects of CXCL1 on MMP2/9 expression. Furthermore, immunohistochemical analysis revealed a strong positive association between CXCL1 and p‑ERK1/2 expression levels in BC tissues. In conclusion, the present study demonstrated that CXCL1 is highly expressed in ER‑negative BC, and stimulates BC cell migration and invasion via the ERK/MMP2/9 pathway. Therefore, CXCL1 may serve as a potential therapeutic target in ER‑negative BC.