首页|CSF2 upregulates CXCL3 expression in adipocytes to promote metastasis of breast cancer via the FAK signaling pathway
CSF2 upregulates CXCL3 expression in adipocytes to promote metastasis of breast cancer via the FAK signaling pathway
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Recent studies have demonstrated that cancer-associated adipocytes(CAAs)in the tumor microenvironment are involved in the malignant progression of breast cancer.However,the underlying mechanism of CAA formation and its effects on the development of breast cancer are still unknown.Here,we show that CSF2 is highly expressed in both CAAs and breast cancer cells.CSF2 promotes inflammatory phenotypic changes of adipocytes through the Stat3 signaling pathway,leading to the secretion of multiple cytokines and proteases,particularly C-X-C motif chemokine ligand 3(CXCL3).Adipocyte-derived CXCL3 binds to its specific receptor CXCR2 on breast cancer cells and activates the FAK pathway,enhancing the mesenchymal phenotype,migration,and invasion of breast cancer cells.In addition,a combination treatment targeting CSF2 and CXCR2 shows a synergistic inhibitory effect on adipocyte-induced lung metastasis of mouse 4T1 cells in vivo.These findings elucidate a novel mechanism of breast cancer metastasis and provide a potential therapeutic strategy for breast cancer metastasis.
breast cancer metastasiscancer-associated adipocytesCSF2CXCL3FAK
Xi He、Lieliang Wang、Honghui Li、Yaru Liu、Chang Tong、Caifeng Xie、Xiaohua Yan、Daya Luo、Xiangyang Xiong
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Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Nanchang University,Nanchang 330006,China
Department of Breast Surgery,Jiangxi Cancer Hospital,Nanchang 330029,China
Pediatric Medical School,Nanchang University,Nanchang 330031,China
Province Key Laboratory of Tumor Pathogens and Molecular Pathology,Nanchang University,Nanchang 330006,China
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National Natural Science Foundation of China(NSFC)National Natural Science Foundation of China(NSFC)Natural Science Foundation of Jiangxi Province of ChinaNatural Science Foundation of Jiangxi Province of China
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