Sacco Jessica L, Gomez Esther W
Department of Chemical Engineering, The Pennsylvania State University, University Park, PA 16802, USA.
Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA 16802, USA.
Cancers (Basel). 2024 Sep 27;16(19):3289. doi: 10.3390/cancers16193289.
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.
肿瘤微环境由多种细胞类型组成，并且随着癌症的进展，其物理和机械特性会发生动态变化。肿瘤内异质性与预后不良相关，并带来治疗挑战，最近的研究已开始确定导致肿瘤内表型多样性的细胞机制。本综述将描述上皮-间质（E/M）可塑性及其对肿瘤表型异质性的贡献，以及表观遗传因素，如组蛋白修饰、组蛋白修饰酶、DNA甲基化和染色质重塑，如何调节和维持E/M表型。本综述还将报告肿瘤间力学特性如何变化以及如何调节表观遗传修饰和E/M可塑性。最后，强调肿瘤内异质性如何影响治疗效果，并提供潜在的治疗靶点以改善癌症治疗。
