2. Academic Validation
  3. Intratumoral bacterium Enterocloster bolteae promotes hepatocellular carcinoma progression by directly binding tumor cells

Intratumoral bacterium Enterocloster bolteae promotes hepatocellular carcinoma progression by directly binding tumor cells

  • Cell Host Microbe. 2026 Mar 11;34(3):406-424.e10. doi: 10.1016/j.chom.2026.01.020.
Xuxin Ren 1,  Gaomin Zheng 1,  Yuyao Liu 1,  Shangru Li 1,  Shimao Liu 1,  Yixi Wen 2,  Ying Zhang 1,  Yutong Zhao 1,  Huayu Guan 3,  Xinning Wang 2,  Yuting Yang 2,  Qiaoyi Chen 1,  Youmei Kang 2,  Yihang Xu 4,  Liting Peng 5,  Sui Peng 6,  Lixia Xu 7,  Jianting Long 8,  Xuezhen Zeng 9,  Shixian Hu 10,  Ming Kuang 11
Affiliations

Affiliations

  • 1 Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 2 Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 3 Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China; Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 4 Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China; Center of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 5 Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China; Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 6 Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China; Clinical Trial Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
  • 7 Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: [email protected].
  • 8 Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: [email protected].
  • 9 Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China; Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: [email protected].
  • 10 Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: [email protected].
  • 11 Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China; Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: [email protected].
PMID: 41742409 DOI: 10.1016/j.chom.2026.01.020
Abstract

The gut microbiota regulates systemic metabolism, inflammation, and immunity, with evidence linking microbiota translocation through the gut-liver axis to hepatocellular carcinoma (HCC) progression. However, the specific bacteria and underlying mechanisms driving tumor progression remain unexplored. We identify that E. bolteae is enriched in the feces of HCC patients and is associated with poor prognosis. E. bolteae disrupts intestinal barrier integrity, translocates to the liver, and promotes tumor proliferation. Mechanistically, we show that E. bolteae's surface protein, penicillin-binding transpeptidase domain-containing protein (PbpT), directly interacts with the tumor cell receptor desmoglein 1 (DSG1), facilitating Bacterial adhesion and attenuating DSG1's tumor-suppressive function. Additionally, this interaction activates the mitogen-activated protein kinase (MAPK) signaling pathway to accelerate HCC progression. Blockade of PbpT abrogates E. bolteae attachment and its role in promoting HCC progression. These findings identify the PbpT-DSG1-MAPK axis as a critical driver of HCC progression. Targeting PbpT may be a promising therapeutic strategy for HCC.

Keywords

Enterocloster bolteae; MAPK signaling pathway; gut-liver axis; hepatocellular carcinoma; intratumoral bacterium.

Figures
Products