Evidence map›Paper›PMID 42766031›Full record

ArticleCellular and molecular life sciences : CMLS2026

Inhibition of EphA2 triggers ferroptosis by disrupting USP38mediated SLC7A11 stabilization in chemoresistant gastric cancer.

Runsha Xiao, Yan Mo, Jin Zhou, Yi Xu, Kuo Kang, Zhikang Chen, Yuanyuan Jiang, Chengmin Li, Xueping Feng, Zihua Chen and 2 more

Abstract read
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In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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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

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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

12 authors.

Runsha XiaoDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China.
Yan MoNational Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Xiangya Hospital, Central South University, Changsha, 410008, China.
Jin ZhouNational Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Xiangya Hospital, Central South University, Changsha, 410008, China.
Yi XuDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China.
Kuo KangDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China.
Zhikang ChenDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China.
Yuanyuan JiangDepartment of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, 410008, China.
Chengmin LiNational Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Xiangya Hospital, Central South University, Changsha, 410008, China.
Xueping FengNational Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Xiangya Hospital, Central South University, Changsha, 410008, China.
Zihua ChenDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China.
Si ChenDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China. chendd0522@163.com.
Chen LaiDepartment of General Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China. 4011333@csu.edu.cn.ORCID http://orcid.org/0000-0002-1516-7036

Funding

Beijing Xisike Clinical Oncology Research Foundation Y-NESTLE2022ZD-0369Natural Science Foundation of Hunan Province 2022JJ30920Natural Science Foundation of Hunan Province 2024JJ5617
6 · The paper itself

Abstract

Aberrant expression of EphA2 (Ephrin receptor A2) in gastric cancer (GC) promotes chemoresistance by suppressing ferroptosis, yet the underlying mechanism remains poorly defined. In this study, we show that EphA2 confers resistance to platinum-based chemotherapy by suppressing ferroptosis through redox homeostasis regulation. Mechanistically, EphA2 directly phosphorylates and activates the deubiquitinase USP38, which in turn stabilizes SLC7A11 by preventing its proteasomal degradation. Elevated SLC7A11 sustains intracellular glutathione homeostasis, attenuates lipid peroxidation, and limits reactive oxygen species accumulation, thereby enabling GC cells to evade ferroptotic cell death under chemotherapeutic stress. Importantly, genetic or pharmacological disruption of the EphA2-USP38 interaction leads to SLC7A11 destabilization, excessive ROS accumulation, ferroptosis induction, and restoration of chemosensitivity. Together, these findings identify the EphA2-USP38/ROS axis as a key determinant of oxaliplatin resistance in GC and highlight a promising therapeutic target for overcoming chemotherapy resistance by reactivating ferroptosis.

Indexed as

Amino Acid Transport System y+Drug Resistance, NeoplasmFerroptosisReceptor, EphA2Stomach NeoplasmsAnimalsAntineoplastic AgentsCell Line, TumorHumansMiceOxaliplatinReactive Oxygen SpeciesAmino Acid Transport System y+Antineoplastic AgentsEPHA2 protein, humanOxaliplatinReactive Oxygen SpeciesReceptor, EphA2SLC7A11 protein, humanChemoresistanceDeubiquitinaseMetabolic reprogrammingMitochondrial damageOxidative stress

Identifiers

PMID42766031
PMCPMC13594076

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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.