Evidence map›Paper›PMID 41980917›Full record

ArticleCell death discovery2026

Targeting the ODC1-YBX1 axis reverses gastric cancer chemoresistance via transcriptional control of SLC7A11-mediated ferroptosis.

Ruiqi Li, Shantanu Baral, Fanyu Zhao, Chenkai Zhang, Jiajie Zhou, Ben Li, Yifan Cheng, Dengyang Fang, Zijie Xu, Yayan Fu and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death discovery, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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

What it found

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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

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

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5 · Who and what money

Authors and funding

19 authors.

Ruiqi LiNorthern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.
Shantanu BaralMedical College of Yangzhou University, Yangzhou, China.
Fanyu ZhaoMedical College of Yangzhou University, Yangzhou, China.
Chenkai ZhangMedical College of Yangzhou University, Yangzhou, China.
Jiajie ZhouNorthern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.
Ben LiNorthern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.
Yifan ChengNorthern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.
Dengyang FangMedical College of Yangzhou University, Yangzhou, China.
Zijie XuNorthern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.
Yayan FuMedical College of Yangzhou University, Yangzhou, China.
Jianyue DingMedical College of Yangzhou University, Yangzhou, China.
Zhen TianNorthern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.
Shuai ZhaoNorthern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.
Jie WangMedical College of Yangzhou University, Yangzhou, China.
Mengli ZiNorthern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.
Longhe SunMedical College of Yangzhou University, Yangzhou, China.
Xuetong JiangThe YangZhou Clinical College of Xuzhou Medical University, Xuzhou, China.
Qiannan SunNorthern Jiangsu People's Hospital, Yangzhou, China.
Daorong WangNorthern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China. wdaorong666@sina.com.

Funding

National Natural Science Foundation of China (National Science Foundation of China) NO.82373014
6 · The paper itself

Abstract

Gastric adenocarcinoma (STAD), a leading cause of cancer mortality, faces major therapeutic challenges due to intrinsic and acquired chemoresistance. Chemoresistance is intricately linked to ferroptosis.Elucidating the mechanisms of chemotherapy resistance in STAD represents a critical unmet need to improve patient survival. This study identifies ODC1 as a crucial driver of 5-Fu resistance and suppressor of ferroptosis in STAD. Multi-dataset analysis revealed significant ODC1 overexpression in STAD tissues, correlating with advanced stage and poor survival. Functionally, ODC1 depletion inhibited proliferation, migration, invasion, and tumor growth in vitro and in vivo, while its overexpression exacerbated malignant phenotypes. Critically, ODC1 was upregulated in 5-Fu-resistant cell models, and its knockdown restored chemosensitivity by triggering ferroptosis-an iron-dependent cell death characterized by lipid peroxidation, glutathione depletion, and malondialdehyde accumulation. Mechanistically, ODC1 interacts with transcription factor YBX1 through its PLPDE_III_ODC domain. This complex binds the promoter of SLC7A11, enhancing its transcription. YBX1 silencing phenocopied ODC1 knockdown, increasing ferroptosis susceptibility; conversely, SLC7A11 overexpression or GPX4 activation (via ML334) reversed ferroptosis induced by ODC1/YBX1 inhibition. Significantly, Erastin-a SLC7A11 inhibitor-overcame YBX1-mediated resistance, synergizing with 5-Fu to induce ferroptosis and suppress tumor growth. Collectively, we unveil the ODC1-YBX1-SLC7A11-ferroptosis axis as a central mechanism of chemoresistance in STAD. Targeting this axis-via ODC1 inhibition or ferroptosis induction-represents a novel therapeutic strategy to reverse treatment resistance in gastric adenocarcinoma.

Identifiers

PMID41980917
PMCPMC13194797

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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.