Streptococcus anginosus-generated succinate promotes the progression of gastric cancer via the succinate/SUCNR1/ABRAXAS1 axis

Foqiang Liao¹, Jianfang Rong¹, Cong He², Taiyu Chen², Linen Li², Yunfeng Huang², Qiang Yang², Jing Guo³, Nianshuang Li², Jianping Liu², Zhongming Ge⁴, Nonghua Lu², Yin Zhu², Xu Shu⁵

Affiliations

¹ Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China; Postdoctoral Innovation Practice Base, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
² Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
³ Department of Dental General and Emergency, the Affiliated Stomatological Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
⁴ Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁵ Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China. Electronic address: ndyfy02016@ncu.edu.cn.

PMID: 41746808
DOI: 10.1016/j.celrep.2026.117047

Streptococcus anginosus-generated succinate promotes the progression of gastric cancer via the succinate/SUCNR1/ABRAXAS1 axis

Foqiang Liao et al. Cell Rep. 2026.

. 2026 Feb 25;45(3):117047.

doi: 10.1016/j.celrep.2026.117047. Online ahead of print.

Authors

Foqiang Liao¹, Jianfang Rong¹, Cong He², Taiyu Chen², Linen Li², Yunfeng Huang², Qiang Yang², Jing Guo³, Nianshuang Li², Jianping Liu², Zhongming Ge⁴, Nonghua Lu², Yin Zhu², Xu Shu⁵

Affiliations

¹ Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China; Postdoctoral Innovation Practice Base, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
² Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
³ Department of Dental General and Emergency, the Affiliated Stomatological Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
⁴ Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁵ Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China. Electronic address: ndyfy02016@ncu.edu.cn.

PMID: 41746808
DOI: 10.1016/j.celrep.2026.117047

Abstract

Streptococcus anginosus (S. anginosus) has recently been implicated in promoting gastric carcinogenesis, but the underlying mechanism of S. anginosus and its metabolites in gastric carcinogenesis is still unclear. We found that S. anginosus is enriched in gastric cancer (GC) and that a high abundance of S. anginosus is associated with a poor prognosis of GC. Both S. anginosus and S. anginosus conditioned medium (S. a CM) promoted the proliferation, invasion, and migration of GC cells, inhibited cell apoptosis in vitro, and aggravated gastric inflammation and mucus metaplasia in vivo. Succinate is identified as the functional metabolite promoting gastric carcinogenesis in S. a CM. Knockdown of succinate receptor 1 (SUCNR1) or treatment with SUCNR1 inhibitors inhibited the tumor-promoting effect of succinate. Mechanistically, S. anginosus-derived succinate binds to SUCNR1 in gastric epithelial cells, and SUCNR1 directly interacts with ABRAXAS1 to activate the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway and promotes the progression of GC.

Keywords: CP: cancer; CP: microbiology; Streptococcus anginosus; gastric carcinogenesis; microbial metabolite; succinate.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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Streptococcus anginosus-generated succinate promotes the progression of gastric cancer via the succinate/SUCNR1/ABRAXAS1 axis

Affiliations

Streptococcus anginosus-generated succinate promotes the progression of gastric cancer via the succinate/SUCNR1/ABRAXAS1 axis

Authors

Affiliations

Abstract

Conflict of interest statement