CXCL13 promotes intestinal tumorigenesis through the activation of epithelial AKT signaling.
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.
['Zhao|Qun|Q|', 'Guo|Jian|J|', 'Wang|Guizhen|G|', 'Bi|Yun|Y|', 'Cheng|Xinran|X|', 'Liao|Yingying|Y|', 'Jin|Shu|S|', 'Li|Lian|L|', 'Guo|Yang|Y|', 'Pan|Longrui|L|', 'Zhang|Xudong|X|', 'Tan|Yan|Y|', 'Zhou|Guangbiao|G|', 'Yu|Xianjun|X|']
D000818:Animals D063646:Carcinogenesis D054382:Chemokine CXCL13 D018925:Chemokines D004195:Disease Models, Animal D005260:Female D006801:Humans D007414:Intestinal Neoplasms D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D051057:Proto-Oncogene Proteins c-akt D015398:Signal Transduction
Chemokines Colorectal cancer Chemokine receptor Dendritic cells Nuclear factor-κB