蛋氨酸
乳腺癌
癌症干细胞
三阴性乳腺癌
癌症研究
癌变
甲基化
癌症
生物
干细胞
化学
生物化学
细胞生物学
氨基酸
遗传学
基因
作者
Cuicui Liu,Lie Chen,Cai Yu-wen,Yufei Chen,Yiming Liu,Yujie Zhou,Zhi‐Ming Shao,Ke‐Da Yu
标识
DOI:10.1016/j.xcrm.2024.101396
摘要
Summary
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.
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