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Updated: Oct 3, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Activation of MAT2A-ACSL3 pathway protects cells from ferroptosis in gastric cancer
Mingzhe Ma1, Pengfei Kong2, Yakai Huang3
1Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Central Laboratory, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, China; Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Background:
Ferroptosis, a unique form of nonapoptotic-regulated cell death caused by overwhelming lipid peroxidation, represents an emerging tumor suppression mechanism. Growing evidence has demonstrated that cell metabolism plays an important role in the regulation of ferroptosis. Specifically, the association between methionine metabolism and ferroptosis remains undefined.
Methods:
We performed in vitro and in vivo experiments to evaluate the influence of methionine metabolism on ferroptosis sensitivity. Pharmacological and genetic blockade of the methionine cycle was utilized and relevant molecular analyses were performed.
Results:
We identified MAT2A as a driver of ferroptosis resistance. Mechanistically, MAT2A mediates the production of S-adenosylmethionine (SAM), which upregulates ACSL3 by increasing the trimethylation of lysine-4 on histone H3 (H3K4me3) at the promoter area, resulting in ferroptosis resistance.
Conclusions:
Collectively, these results established a link between methionine cycle activity and ferroptosis vulnerability in gastric cancer.
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