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

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

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
22 Jan 2024
Historique:
received: 08 08 2022
revised: 13 10 2023
accepted: 02 01 2024
medline: 1 2 2024
pubmed: 1 2 2024
entrez: 31 1 2024
Statut: aheadofprint

Résumé

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.

Identifiants

DOI: 10.1016/j.cell.2024.01.004 PMID: 38295787
pubmed: 38295787
pii: S0092-8674(24)00006-0
doi: 10.1016/j.cell.2024.01.004
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Kaili Fu (K)

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.

Alvin Ho Kwan Cheung (AHK)

Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China.

Chi Chun Wong (CC)

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.

Weixin Liu (W)

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.

Yunfei Zhou (Y)

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.

Feixue Wang (F)

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.

Pingmei Huang (P)

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.

Kai Yuan (K)

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.

Olabisi Oluwabukola Coker (OO)

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.

Yasi Pan (Y)

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.

Danyu Chen (D)

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.

Nga Man Lam (NM)

Department of Microbiology, The Chinese University of Hong Kong, Hong Kong SAR, China.

Mengxue Gao (M)

Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.

Xiang Zhang (X)

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.

He Huang (H)

Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.

Ka Fai To (KF)

Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China.

Joseph Jao Yiu Sung (JJY)

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: josephsung@ntu.edu.sg.

Jun Yu (J)

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: junyu@cuhk.edu.hk.

Classifications MeSH