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  3. Catenibacteriummitsuokai promotes hepatocellular carcinogenesis by binding to hepatocytes and generating quinolinic acid

Catenibacteriummitsuokai promotes hepatocellular carcinogenesis by binding to hepatocytes and generating quinolinic acid

  • Cell Metab. 2025 Oct 7;37(10):1998-2013.e7. doi: 10.1016/j.cmet.2025.09.001.
Ying Zhang 1,  Weixin Liu 2,  Chi Chun Wong 2,  Qian Song 2,  Xinyue Zhang 3,  Qianying Zhou 3,  Xuxin Ren 3,  Xiaoxue Ren 3,  Ruiyan Xuan 3,  Yutong Zhao 3,  Linfu Xu 4,  Xiaoxing Li 4,  Lixia Xu 3,  Xiang Zhang 2,  Ming Kuang 5,  Jun Yu 6
Affiliations

Affiliations

  • 1 Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • 2 Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • 3 Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • 4 Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • 5 Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: kuangm@mail.sysu.edu.cn.
  • 6 Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: junyu@cuhk.edu.hk.
PMID: 41005296 DOI: 10.1016/j.cmet.2025.09.001
Abstract

The role of gut microbes in the pathogenesis of hepatocellular carcinoma (HCC) remains unclear. Here, we identified that Catenibacterium is enriched in both the feces and tumors of patients with HCC. C. mitsuokai accelerated HCC carcinogenesis in both conventional and germ-free mice. Furthermore, C. mitsuokai disrupted the gut barrier and translocated to the liver as live bacteria. Critically, the C. mitsuokai surface protein Gtr1/RagA interacts with the γ-catenin receptor on HCC cells, facilitating its attachment and colonization in the mouse liver. We further revealed that the pro-tumorigenic effect of C. mitsuokai depends on its secreted metabolite, quinolinic acid. Mechanistically, quinolinic acid binds to and activates the tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 (Tie2) on HCC cells. Phosphorylated Tie2 subsequently activates the downstream oncogenic phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway, thereby promoting HCC progression. In summary, C. mitsuokai disrupts the gut barrier, colonizes HCC cells via Gtr1/RagA-γ-catenin, and secretes quinolinic acid, which binds to Tie2 and drives the PI3K/Akt pathway to promote HCC development.

Keywords

C. mitsuokai; Gtr1/RagA; hepatocellular carcinoma; quinolinic acid.

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