Malonyl-CoA Promotes Prostate Cancer Progression and Castration Resistance by Enhancing Lipogenesis and Ran Activation
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Le résumé fourni par la source
Malonyl-CoA, a key metabolite, is not only the building block for lipogenesis but also a critical regulator of mitochondrial fatty acid β-oxidation. Given the altered metabolic state of many cancers, malonyl-CoA may play a role in tumor development and drug resistance, especially in malignancies characterized by abnormal lipid metabolism, such as prostate cancer. In this study, we showed that the levels of malonyl-CoA were increased in prostate cancer, especially in castration-resistant prostate cancer. Abnormal accumulation of malonyl-CoA promoted lipogenesis and regulated metabolic processes, maintaining endoplasmic reticulum homeostasis and mitochondrial function and ultimately contributing to prostate cancer progression. Restoration of malonyl-CoA decarboxylase expression activated the unfolded protein response via the consumption of malonyl-CoA. Importantly, malonyl-CoA accumulation promoted lysine malonylation in prostate cancer. Ran K141 malonylation increased Ran activity and enhanced androgen receptor nuclear translocation and transcriptional activity, ultimately contributing to prostate cancer development and resistance to antiandrogens. These findings highlight the function of malonyl-CoA in prostate cancer progression by regulating metabolic processes and malonylating Ran K141, revealing that the malonyl-CoA axis might be a reliable biomarker and a potential therapeutic target in prostate cancer. SIGNIFICANCE: Malonyl-CoA induces metabolic reprogramming and Ran-mediated androgen receptor activation to support prostate cancer development and drug resistance, providing a mechanism that could be harnessed for developing treatment strategies for advanced prostate cancer.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Malonyl-CoA Promotes Prostate Cancer Progression and Castration Resistance by Enhancing Lipogenesis and Ran Activation
- Date Crossref
- 27/08/2025
- Éditeur
- American Association for Cancer Research (AACR)
- 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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First Affiliated Hospital of Zhengzhou University Henan Institute of Urology and Zhengzhou Key Laboratory for Molecular Biology of Urological Tumor Research pays non établi dans la noticeÉtablissement de santé
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Tongji Hospital pays non établi dans la noticeÉtablissement de santé
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Huazhong University of Science and Technology pays non établi dans la noticeUniversité ou école supérieure
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Wuhan Union Hospital pays non établi dans la noticeÉtablissement de santé
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Union Hospital pays non établi dans la noticeÉtablissement de santé
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Shenzhen Second People's Hospital pays non établi dans la noticeÉtablissement de santé
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Tongji Medical College Tongji Hospital pays non établi dans la noticeUniversité ou école supérieure
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The Second Clinic Medical College of Jinan University Shenzhen People’s Hospital pays non établi dans la noticeUniversité ou école supérieure
Henan Institute of Urology and Zhengzhou Key Laboratory for Molecular Biology of Urological Tumor Research — First Affiliated Hospital of Zhengzhou University, Tongji Hospital et Huazhong University of Science and Technology, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.