2. Academic Validation
  3. Streptococcus anginosus promotes gastric inflammation, atrophy, and tumorigenesis in mice

Streptococcus anginosus promotes gastric inflammation, atrophy, and tumorigenesis in mice

  • Cell. 2024 Feb 15;187(4):882-896.e17. doi: 10.1016/j.cell.2024.01.004.
Kaili Fu 1,  Alvin Ho Kwan Cheung 2,  Chi Chun Wong 1,  Weixin Liu 1,  Yunfei Zhou 1,  Feixue Wang 1,  Pingmei Huang 1,  Kai Yuan 1,  Olabisi Oluwabukola Coker 1,  Yasi Pan 1,  Danyu Chen 1,  Nga Man Lam 3,  Mengxue Gao 4,  Xiang Zhang 1,  He Huang 4,  Ka Fai To 2,  Joseph Jao Yiu Sung 5,  Jun Yu 6
Affiliations

Affiliations

  • 1 Institute of Digestive Disease and Department of Medicine and Therapeutics, 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 Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • 3 Department of Microbiology, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • 4 Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.
  • 5 Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. Electronic address: [email protected].
  • 6 Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China. Electronic address: [email protected].
PMID: 38295787 DOI: 10.1016/j.cell.2024.01.004
Abstract

Streptococcus anginosus (S. anginosus) was enriched in the gastric mucosa of patients with gastric Cancer (GC). Here, we show that S. anginosus colonized the mouse stomach and induced acute gastritis. S. anginosus Infection spontaneously induced progressive chronic gastritis, parietal cell atrophy, mucinous metaplasia, and dysplasia in conventional mice, and the findings were confirmed in germ-free mice. In addition, S. anginosus accelerated GC progression in carcinogen-induced gastric tumorigenesis and YTN16 GC cell allografts. Consistently, S. anginosus disrupted gastric barrier function, promoted cell proliferation, and inhibited Apoptosis. Mechanistically, we identified an S. anginosus surface protein, TMPC, that interacts with Annexin A2 (AnxA2) receptor on gastric epithelial cells. Interaction of TMPC with AnxA2 mediated attachment and colonization of S. anginosus and induced mitogen-activated protein kinase (MAPK) activation. AnxA2 knockout abrogated the induction of MAPK by S. anginosus. Thus, this study reveals S. anginosus as a pathogen that promotes gastric tumorigenesis via direct interactions with gastric epithelial cells in the TMPC-ANXA2-MAPK axis.

Keywords

MAPK signaling; Streptococcus anginosus; gastric cancer; germ-free mice; surface protein.

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