Laboratory of Inflammation and Molecular Pharmacology, School of Basic Medical Sciences & Biomedical Research Institute, Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan 442000, China; State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Laboratory of Inflammation and Molecular Pharmacology, School of Basic Medical Sciences & Biomedical Research Institute, Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan 442000, China.
Cancer Lett. 2021 Jul 28;511:1-14. doi: 10.1016/j.canlet.2021.04.012. Epub 2021 Apr 22.
The excessive release of proinflammatory chemokines promotes cell proliferation and tumor growth in colorectal cancer. However, their regulatory functions and molecular pathogenesis have not been well elucidated. Here, we observed the upregulation of chemokine (C-X-C motif) ligand 13 (CXCL13) in human colorectal cancers and mouse intestinal tumors. Both CXCL13 deficiency and blockade of CXCL13 signaling ameliorated disease progression. CXCL13 promoted intestinal tumorigenesis through the activation of the AKT signaling pathway in a C-X-C chemokine receptor type 5 (CXCR5)-dependent manner. Intestinal microbiota translocation drove CXCL13 production in dendritic cells through the activation of NF-κB signaling. Inhibition of microbiota translocation decreased CXCL13 production and ameliorated intestinal tumorigenesis. Together, the results of this study identify a role for the CXCL13-CXCR5 axis is involved in the crosstalk between chemokines and cell growth during the development of intestinal tumorigenesis, which also provides a therapeutic strategy for targeting CXCL13/CXCR5 in the future clinical treatment of intestinal tumors.
趋化因子（C-X-C 基序）配体 13（CXCL13）在人结直肠癌和小鼠肠道肿瘤中的过度表达。CXCL13 缺乏和阻断 CXCL13 信号均改善了疾病进展。CXCL13 通过 CXCR5 依赖性方式激活 AKT 信号通路促进肠道肿瘤发生。肠道微生物群易位通过激活 NF-κB 信号通路在树突状细胞中驱动 CXCL13 的产生。抑制微生物群易位可减少 CXCL13 的产生并改善肠道肿瘤发生。总之，本研究结果表明，CXCL13-CXCR5 轴在肠道肿瘤发生过程中细胞生长和趋化因子之间的串扰中起作用，这也为未来肠道肿瘤的临床治疗中靶向 CXCL13/CXCR5 提供了一种治疗策略。
