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April 30, 2026Cell DiscoveryOpen Access

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

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Authors

JBJunping BaiDGDandan GengXCXinwen Chen

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Overview

Untargeted metabolomics reveals serotonin promotes tumor growth via GPX4 serotonylation, suggesting a novel therapeutic target in gastric cancer.

Key Points

  • This research aims to investigate the role of protein serotonylation in gastric tumorigenesis, focusing on TGM2 and GPX4.
  • Utilized untargeted plasma metabolomics to assess serotonin levels in gastric cancer patients.
  • Conducted proliferation assays to evaluate the effects of serotonin on GC cell growth.
  • Employed a 5-HT-based chemoproteomic approach to identify serotonylation targets.
  • Analyzed correlations between TGM2 and GPX4 expression levels in clinical specimens.
  • 5-HT levels were significantly elevated in gastric cancer patients, promoting cell proliferation and tumor growth.
  • Inhibition of TGM2 abrogated the oncogenic effects of serotonin, highlighting its role in tumorigenesis.
  • GPX4 was identified as a key serotonylation target, with serotonylation increasing its stability against degradation.
  • TGM2 levels positively correlated with GPX4 expression in gastric cancer tissue.

Cite This Study

Bai et al. (2026) studied this question.

synapsesocial.com/papers/69f2a4da8c0f03fd67763ec1https://doi.org/10.1038/s41421-026-00885-6
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