表观遗传学修饰在癌症相关成纤维细胞中的作用
The role of epigenetic modifications in cancer-associated fibroblasts.
摘要(中文译文)
肿瘤相关成纤维细胞（cancer-associated fibroblasts，CAFs）构成了一群异质性的基质细胞群体，其肿瘤调控活性高度依赖于具体情境。与癌细胞不同，CAFs很少携带稳定的基因突变；相反，其表型可塑性在很大程度上由可逆的表观遗传重编程所驱动。在肿瘤微环境（tumor microenvironment，TME）中，CAFs作为关键调控因子，通过分泌细胞外基质（extracellular matrix，ECM）成分、旁分泌生长因子、细胞因子及代谢中间产物，共同促进肿瘤生长、侵袭和治疗耐药。近年来肿瘤生物学的进展已将关注点从单纯编目编码序列突变转向理解塑造CAF身份与功能的表观遗传机制。主要的表观遗传调控机制包括DNA甲基化、组蛋白修饰和RNA修饰，它们在不改变 underlying DNA序列的情况下动态调控染色质结构和基因表达。新出现的证据表明，CAFs的激活和功能异质性主要由这些表观遗传改变而非永久性遗传变化所主导。表观遗传重编程使CAFs能够获得多种促肿瘤特性，包括重塑细胞外基质、调节细胞间信号通路以及分泌影响邻近癌细胞和免疫细胞基因表达的细胞因子。这些过程最终促进肿瘤发生、进展、转移和治疗耐药。本综述总结了关于表观遗传修饰如何调控肿瘤微环境中CAF激活与功能的最新研究进展。此外，我们还讨论了靶向CAF相关表观遗传通路作为癌症治疗有前景的治疗策略的潜力。
Abstract
Cancer-associated fibroblasts (CAFs) constitute a heterogeneous population of stromal cells whose tumor-modulating activities are highly context-dependent. Unlike cancer cells, CAFs rarely harbor stable genetic mutations; instead, their phenotypic plasticity is largely driven by reversible epigenetic reprogramming. Within the tumor microenvironment (TME), CAFs function as key regulators by secreting extracellular matrix (ECM) components, paracrine growth factors, cytokines, and metabolic intermediates that collectively promote tumor growth, invasion, and therapeutic resistance. Recent advances in cancer biology have shifted attention from solely cataloging coding-sequence mutations toward understanding the epigenetic mechanisms that shape CAF identity and function. Major epigenetic regulatory mechanisms include DNA methylation, histone modifications, and RNA modifications, which dynamically regulate chromatin structure and gene expression without altering the underlying DNA sequence. Emerging evidence indicates that the activation and functional heterogeneity of CAFs are predominantly governed by these epigenetic alterations rather than by permanent genetic changes. Epigenetic reprogramming enables CAFs to acquire diverse tumor-promoting properties, including remodeling of the extracellular matrix, modulation of intercellular signaling pathways, and secretion of cytokines that influence gene expression in neighboring cancer and immune cells. These processes ultimately contribute to tumor initiation, progression, metastasis, and resistance to therapy. This review summarizes recent advances in understanding how epigenetic modifications regulate CAF activation and function within the tumor microenvironment. In addition, we discuss the potential of targeting CAF-associated epigenetic pathways as a promising therapeutic strategy for cancer treatment.
如何引用
AMA
Binghang Yan, Chengxiao Yang, Xinyuan Liu, Qinwen Zuo, Jing Wang, Wenbo Yang, et al. The role of epigenetic modifications in cancer-associated fibroblasts.. Frontiers in medicine. 2026; doi:10.3389/fmed.2026.1780734.
APA
Binghang Yan, Chengxiao Yang, Xinyuan Liu, Qinwen Zuo, Jing Wang, Wenbo Yang, et al (2026). The role of epigenetic modifications in cancer-associated fibroblasts.. Frontiers in medicine. https://doi.org/10.3389/fmed.2026.1780734
GB/T 7714
Binghang Yan, Chengxiao Yang, Xinyuan Liu, Qinwen Zuo, Jing Wang, Wenbo Yang, et al. The role of epigenetic modifications in cancer-associated fibroblasts.[J]. Frontiers in medicine, 2026 doi:10.3389/fmed.2026.1780734.
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