The tumor microenvironment comprises various cell types and experiences dynamic alterations in physical and mechanical properties as cancer progresses. Intratumoral heterogeneity is associated with poor prognosis and poses therapeutic challenges, and recent studies have begun to identify the cellular mechanisms that contribute to phenotypic diversity within tumors. This review will describe epithelial–mesenchymal (E/M) plasticity and its contribution to phenotypic heterogeneity in tumors as well as how epigenetic factors, such as histone modifications, histone modifying enzymes, DNA methylation, and chromatin remodeling, regulate and maintain E/M phenotypes. This review will also report how mechanical properties vary across tumors and regulate epigenetic modifications and E/M plasticity. Finally, it highlights how intratumoral heterogeneity impacts therapeutic efficacy and provides potential therapeutic targets to improve cancer treatments.
肿瘤微环境包含多种细胞类型，并在癌症进展过程中经历物理和机械特性的动态变化。瘤内异质性与不良预后相关，并带来治疗挑战，近期研究已开始揭示导致肿瘤内表型多样性的细胞机制。本综述将阐述上皮-间质（E/M）可塑性及其对肿瘤表型异质性的贡献，以及组蛋白修饰、组蛋白修饰酶、DNA甲基化和染色质重塑等表观遗传因素如何调控和维持E/M表型。同时将论述肿瘤中机械特性的空间差异如何调节表观遗传修饰和E/M可塑性。最后，重点探讨瘤内异质性对治疗效果的影响，并提出改善癌症治疗的潜在治疗靶点。
Epithelial–Mesenchymal Plasticity and Epigenetic Heterogeneity in Cancer
肿瘤(癌症)患者之家