Evidence map›Paper›PMID 42049702›Full record

ArticleCell discovery2026

TGM2-mediated serotonylation of GPX4 confers ferroptosis resistance to promote gastric tumorigenesis.

Junping Bai, Dandan Geng, Xinwen Chen, Wanting Li, Xiaowei Wang, Luyang Tian, Yi Han, Zhao Jin, Meihang Du, Yang Tang and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell discovery, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors.

Junping Bai *Department of Stomatology, Shanghai Tenth People's Hospital, Department of Biochemistry and Molecular Biology, Tongji University Cancer Center, School of Medicine, Tongji University, Shanghai, China.
Dandan Geng *School of Medicine, Anhui University of Science and Technology, Huainan, Anhui, China.
Xinwen Chen *Department of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, China.
Wanting Li *School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China.
Xiaowei WangDepartment of Stomatology, Shanghai Tenth People's Hospital, Department of Biochemistry and Molecular Biology, Tongji University Cancer Center, School of Medicine, Tongji University, Shanghai, China.
Luyang TianState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
Yi HanDepartment of Stomatology, Shanghai Tenth People's Hospital, Department of Biochemistry and Molecular Biology, Tongji University Cancer Center, School of Medicine, Tongji University, Shanghai, China.
Zhao JinInstitutes of Biomedical Sciences, Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, China.
Meihang DuDepartment of Stomatology, Shanghai Tenth People's Hospital, Department of Biochemistry and Molecular Biology, Tongji University Cancer Center, School of Medicine, Tongji University, Shanghai, China.
Yang TangDepartment of Stomatology, Shanghai Tenth People's Hospital, Department of Biochemistry and Molecular Biology, Tongji University Cancer Center, School of Medicine, Tongji University, Shanghai, China.
Weisheng HuShanghai Bioprofile Technolgy Co. Ltd, Shanghai, China.
Chunxiao ZhuState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
Shan ZhangDepartment of Stomatology, Shanghai Tenth People's Hospital, Department of Biochemistry and Molecular Biology, Tongji University Cancer Center, School of Medicine, Tongji University, Shanghai, China.
Zhangting ZhaoDepartment of Stomatology, Shanghai Tenth People's Hospital, Department of Biochemistry and Molecular Biology, Tongji University Cancer Center, School of Medicine, Tongji University, Shanghai, China.
Run ZhangState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
Xinru ZhangDepartment of Stomatology, Shanghai Tenth People's Hospital, Department of Biochemistry and Molecular Biology, Tongji University Cancer Center, School of Medicine, Tongji University, Shanghai, China.
Wei KangDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, State Key Laboratory of Digestive Disease, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.ORCID http://orcid.org/0000-0002-4651-677X
KaFai ToDepartment of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, State Key Laboratory of Digestive Disease, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.
Sachiyo NomuraDepartment of Gastrointestinal surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Fenghua GuoDepartment of General Surgery, Huashan Hospital, Fudan University Shanghai Medical College, Shanghai, China.
Shi JiaoState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0003-3591-8973
Yixuan XieNHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Zhaocai ZhouState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China. zhouzhaocai@fudan.edu.cn.
Chao DongDepartment of Medical Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. dcayy_2008@163.com.
Hui LiDepartment of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, China. lihui05@tmu.edu.cn.
Liwei AnDepartment of Stomatology, Shanghai Tenth People's Hospital, Department of Biochemistry and Molecular Biology, Tongji University Cancer Center, School of Medicine, Tongji University, Shanghai, China. lwan@tongji.edu.cn.

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82222052National Natural Science Foundation of China (National Science Foundation of China) 82573553Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission) 23ZR1480400
6 · The paper itself

Abstract

Protein monoaminylation represents a new layer of neural-cancer regulation, but its role in gastric tumorigenesis is not understood. Using untargeted plasma metabolomics, we revealed that the level of serotonin (5-HT) is significantly elevated in gastric cancer (GC) patients. Functionally, 5-HT treatment dramatically promoted GC cell proliferation and tumor growth in a dose-dependent manner. Importantly, this oncogenic effect was abrogated by the inhibition of transglutaminase 2 (TGM2), indicating a crucial role for protein serotonylation via a receptor-independent mechanism. Using a 5-HT-based chemoproteomic probe, we identified a broad spectrum of serotonylation targets, including key ferroptosis-related proteins such as glutathione peroxidase 4 (GPX4). Specifically, we found that GPX4 is serotonylated by TGM2 at residues Gln55 and Gln77, which increases GPX4 protein stability by attenuating its ubiquitin-mediated degradation, thereby conferring resistance to ferroptosis and facilitating tumor growth. Clinically, TGM2 levels were positively correlated with tumoral GPX4 expression in GC patient specimens. Collectively, our results establish TGM2-mediated GPX4 serotonylation as a key mechanism driving GC progression through ferroptosis resistance, highlighting its potential as both a diagnostic biomarker and a therapeutic target within the neural-tumor axis.

Identifiers

PMID42049702
PMCPMC13125317

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.