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 mechanism in estrogen receptor α (ER) negative breast cancer (BC) has little been known. In this study, we discovered that CXCL1 is overexpression in ER-negative breast cancer tissues and cell lines compared with ER-positive patient tissues and cell lines. Treatment with recombinant human CXCL1 protein promotes ER-negative BC cell migration and invasion in dose-dependent manner and stimulates the activation of p-ERK1/2, but not p-STAT3 or p-AKT. Whereas, knockdown of CXCL1 in BC cells attenuates these effects. Moreover, CXCL1 induces the expression of MMP2/9 via ERK1/2 pathway. The blockage of ERK by its antagonists (U0126) can abolish the effect of CXCL1 on MMP2/9 expression. Furthermore, immunohistochemical (IHC) analysis revealsa strong positive correlation between CXCL1 and p-ERK1/2 expressions in BC tissues. In conclusion, our study illustrates that CXCL1 is highly expressed in ER-negative BC and stimulates cell migration and invasion through ERK/MMP2/9 pathway, which may serve as a potential therapeutictarget in ER-negative breast cancer.

Citation Format: Liu S, Yang C, Guo S, Chen R. CXCL1 chemokine stimulates migration and invasion in ER-negative breast cancer through activation of the ERK/MMP-2/9 signaling axis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-09-06.