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

Abstract

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.

AP-2γ is Required for Maintenance of Pluripotent Mammary Stem Cells

“…The Cxcl1 gene encodes chemokine (C-X-C motif) ligand 1, which is a member of the chemokine family involved in inflammation and tumor progression (Dhawan and Richmond, 2002). Cxcl1 is up-regulated in ERa-negative breast cancer and stimulates migration and tumor invasiveness through Erk1/2 activation (Yang et al, 2019). Breast cancers with overexpression of CXCL1 have increased propensity for survival at metastatic sites and demonstrate chemoresistance (Acharyya et al, 2012).…”

Prognostic and Clinicopathological Significance of CXCL1 Expression in Gastric Cancer: A Meta-Analysis.

“…Numerous studies have shown that CXCL1 could promote the progression of cancer by activating multiple signaling pathways. Yang et al revealed that high expression of CXCL1 stimulated breast cancer cell metastasis via the ERK/MMP2/9 pathway [12]. Wang et al discovered CXCL1 promoted breast cancer metastasis via NF-kB/SOX4 activation [18].…”

“…CXCL1 binds speci cally to the CXC chemokine receptor 2 (CXCR2), which is a member of the G protein-coupled receptor superfamily [9]. Previous investigations have demonstrated CXCL1 expression might play an essential role in the chemoresistance, tumorigenesis, metastasis and angiogenesis of cancer [10][11][12][13]. In recent years, previous studies had explored the prognostic effects of CXCL1 in cancers [14][15][16][17][18][19][20][21][22].…”

Hyaluronic acid optimizes therapeutic effects of Hydrogen peroxide-induced oxidative stress on breast cancer

“…MMP-2 and 9 are regarded as markers of metastatic potential in malignancies (39). The level of these two markers were evaluated in 4T1 cells following treatment with H 2 O 2 or H 2 O 2 + HA as oxygen source.…”