2. Academic Validation
  3. CXCL13 promotes intestinal tumorigenesis through the activation of epithelial AKT signaling

CXCL13 promotes intestinal tumorigenesis through the activation of epithelial AKT signaling

  • Cancer Lett. 2021 Jul 28;511:1-14. doi: 10.1016/j.canlet.2021.04.012.
Qun Zhao 1,  Jian Guo 2,  Guizhen Wang 3,  Yun Bi 2,  Xinran Cheng 2,  Yingying Liao 4,  Shu Jin 5,  Lian Li 6,  Yang Guo 2,  Longrui Pan 2,  Xudong Zhang 2,  Yan Tan 2,  Guangbiao Zhou 7,  Xianjun Yu 8
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 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.
  • 4 Department of Gastroenterology, Renming Hospital, Hubei University of Medicine, Shiyan 442000, China.
  • 5 Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China.
  • 6 Department of Clinical Laboratory Medicine, Renming Hospital, Hubei University of Medicine, Shiyan 442000, China.
  • 7 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. Electronic address: gbzhou@cicams.ac.cn.
  • 8 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. Electronic address: xjyu@hbmu.edu.cn.
PMID: 33894331 DOI: 10.1016/j.canlet.2021.04.012
Abstract

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.

Keywords

Chemokine receptor; Chemokines; Colorectal cancer; Dendritic cells; Nuclear factor-κB.

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