دورية أكاديمية
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Targeting EMSY-mediated methionine metabolism is a potential therapeutic strategy for triple-negative breast cancer.

التفاصيل البيبلوغرافية
العنوان: Targeting EMSY-mediated methionine metabolism is a potential therapeutic strategy for triple-negative breast cancer.
المؤلفون: Liu CC; Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center and Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China., Chen L; Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center and Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China., Cai YW; Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center and Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China., Chen YF; Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center and Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China., Liu YM; Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center and Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China., Zhou YJ; Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center and Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China., Shao ZM; Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center and Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China., Yu KD; Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center and Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China. Electronic address: yukeda@fudan.edu.cn.
المصدر: Cell reports. Medicine [Cell Rep Med] 2024 Feb 20; Vol. 5 (2), pp. 101396. Date of Electronic Publication: 2024 Jan 29.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101766894 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-3791 (Electronic) Linking ISSN: 26663791 NLM ISO Abbreviation: Cell Rep Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, [2020]-
مواضيع طبية MeSH: Triple Negative Breast Neoplasms*/drug therapy , Triple Negative Breast Neoplasms*/genetics , Triple Negative Breast Neoplasms*/metabolism, Humans ; Cell Line, Tumor ; Neoplasm Recurrence, Local
مستخلص: Cancer stem cells (CSCs) are the most intractable subpopulation of triple-negative breast cancer (TNBC) cells, which have been associated with a high risk of relapse and poor prognosis. However, eradication of CSCs continues to be difficult. Here, we integrate the multiomics data of a TNBC cohort (n = 360) to identify vital markers of CSCs. We discover that EMSY, inducing a BRCAness phenotype, is preferentially expressed in breast CSCs, promotes ALDH + cells enrichment, and is positively correlated with poor relapse-free survival. Mechanistically, EMSY competitively binds to the Jmjc domain, which is critical for KDM5B enzyme activity, to reshape methionine metabolism, and to promote CSC self-renewal and tumorigenesis in an H3K4 methylation-dependent manner. Moreover, EMSY accumulation in TNBC cells sensitizes them to PARP inhibitors against bulk cells and methionine deprivation against CSCs. These findings indicate that clinically relevant eradication of CSCs could be achieved with a strategy that targets CSC-specific vulnerabilities in amino acid metabolism.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
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فهرسة مساهمة: Keywords: EMSY; KDM5B; PARP inhibitors; cancer stem cells; methionine metabolism
تواريخ الأحداث: Date Created: 20240130 Date Completed: 20240223 Latest Revision: 20240229
رمز التحديث: 20240229
مُعرف محوري في PubMed: PMC10897545
DOI: 10.1016/j.xcrm.2024.101396
PMID: 38290515
قاعدة البيانات: MEDLINE
الوصف
تدمد:2666-3791
DOI:10.1016/j.xcrm.2024.101396