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

被引：113

作者：

Fu, Kaili ^{[1
,2
]}

Cheung, Alvin Ho Kwan ^{[3
]}

Wong, Chi Chun ^{[1
,2
]}

Liu, Weixin ^{[1
,2
]}

Zhou, Yunfei ^{[1
,2
]}

Wang, Feixue ^{[1
,2
]}

Huang, Pingmei ^{[1
,2
]}

Yuan, Kai ^{[1
,2
]}

Coker, Olabisi Oluwabukola ^{[1
,2
]}

Pan, Yasi ^{[1
,2
]}

Chen, Danyu ^{[1
,2
]}

Lam, Nga Man ^{[4
]}

Gao, Mengxue ^{[5
]}

Zhang, Xiang ^{[1
,2
]}

Huang, He ^{[5
]}

To, Ka Fai ^{[3
]}

Sung, Joseph Jao Yiu ^{[1
,2
,6
]}

Yu, Jun ^{[1
,2
]}

机构：

[1] Chinese Univ Hong Kong, Inst Digest Dis, Hong Kong, Peoples R China

[2] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, State Key Lab Digest Dis, Dept Med & Therapeut, Hong Kong, Peoples R China

[3] Chinese Univ Hong Kong, Dept Anat & Cellular Pathol, Hong Kong, Peoples R China

[4] Chinese Univ Hong Kong, Dept Microbiol, Hong Kong, Peoples R China

[5] Tianjin Univ, Sch Chem Engn & Technol, Dept Biochem Engn, Tianjin, Peoples R China

[6] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore

来源：

CELL | 2024年 / 187卷 / 04期

关键词：

ACTIVATION; CLAUDIN-18; RECEPTOR; REVEALS; STOMACH; PATHWAY;

D O I：

10.1016/j.cell.2024.01.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：882 / 896.e17

页数：33

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