EFNA4-enhanced deubiquitination of SLC7A11 inhibits ferroptosis in hepatocellular carcinoma
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Le résumé fourni par la source
EFNA4, a member of the Ephrin-A ligand family, may influence hepatocellular carcinoma cells through two distinct mechanisms: one reliant on specific Eph receptor binding and the other independent of receptor involvement. However, EFNA4's influence on HCC via non-Eph receptor pathways remains unclear. In this study, we aimed to investigate the role of EFNA4 in a receptor-independent environment. Firstly, we constructed an environment lacking Eph receptors via CRISPR/Cas9 and found that EFNA4 could still partially promote HCC proliferation and metastasis in vivo and in vitro. Further analyses of apoptosis, ROS, and GPX4 expression revealed that overexpression of EFNA4 would inhibit ferroptosis in HCC. Mechanistically, EFNA4 was positively correlated with SLC7A11 and directly interacted with SLC7A11 in HCC via bioinformatics analysis. We demonstrated that the structural domain (a.a. 161-201) of EFNA4 specifically binds to the domain (a.a. 222-501) of SLC7A11, which led to the deubiquitination of SLC7A11. Subsequently, we found that EFNA4 would recruit the deubiquitinase USP9X, resulting in inhibition of SLC7A11 degradation, which ultimately inhibits ferroptosis and enhances the proliferation and metastasis of HCC. In conclusion, we demonstrated that EFNA4 promotes the proliferation and metastasis of HCC independent of Eph receptors by inhibiting ferroptosis and advancing the deubiquitination of SLC7A11 by recruiting the deubiquitinase USP9X. This indicates that EFNA4 could act as a potential prognostic marker and a prospective therapeutic target in patients with HCC.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- EFNA4-enhanced deubiquitination of SLC7A11 inhibits ferroptosis in hepatocellular carcinoma
- Date Crossref
- 10/12/2024
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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TCM-Intigrated Cancer Center of Southern Medical University pays non établi dans la noticeÉtablissement de santé
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Central South University Department of Pulmonary and Critical Care Medicine pays non établi dans la noticeUniversité ou école supérieure
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The First People's Hospital of Changde pays non établi dans la noticeÉtablissement de santé
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Third Xiangya Hospital pays non établi dans la noticeÉtablissement de santé
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Fudan University pays non établi dans la noticeUniversité ou école supérieure
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Zhongshan Hospital of Xiamen University pays non établi dans la noticeÉtablissement de santé
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Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine pays non établi dans la noticeUniversité ou école supérieure
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Xiangya School of Medicine Changde Hospital pays non établi dans la noticeUniversité ou école supérieure
TCM-Intigrated Cancer Center of Southern Medical University, Department of Pulmonary and Critical Care Medicine — Central South University et The First People's Hospital of Changde, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.