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癌症相关成纤维细胞:乳腺癌中的表观遗传调控与治疗干预

Cancer-Associated Fibroblasts: Epigenetic Regulation and Therapeutic Intervention in Breast Cancer.

作者信息

Lee Yeuan Ting, Tan Yi Jer, Falasca Marco, Oon Chern Ein

机构信息

Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Penang 11800, Malaysia.

Metabolic Signalling Group, School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia.

出版信息

Cancers (Basel). 2020 Oct 13;12(10):2949. doi: 10.3390/cancers12102949.

Abstract

Breast cancer is the leading cause of cancer-related mortality in women worldwide. Cancer-associated fibroblasts (CAFs) are a heterogeneous population of cells in the solid tumour microenvironment. These cells are positively linked to breast cancer progression. Breast CAFs can be categorised into distinct subtypes according to their roles in breast carcinogenesis. Epigenetic modifications change gene expression patterns as a consequence of altered chromatin configuration and DNA accessibility to transcriptional machinery, without affecting the primary structure of DNA. Epigenetic dysregulation in breast CAFs may enhance breast cancer cell survival and ultimately lead to therapeutic resistance. A growing body of evidence has described epigenetic modulators that target histones, DNA, and miRNA as a promising approach to treat cancer. This review aims to summarise the current findings on the mechanisms involved in the epigenetic regulation in breast CAFs and discusses the potential therapeutic strategies via targeting these factors.

摘要

乳腺癌是全球女性癌症相关死亡的主要原因。癌症相关成纤维细胞(CAFs)是实体瘤微环境中一类异质性细胞群体。这些细胞与乳腺癌进展呈正相关。乳腺CAFs可根据其在乳腺癌发生中的作用分为不同亚型。表观遗传修饰由于染色质构型改变和DNA对转录机制的可及性改变而改变基因表达模式,而不影响DNA的一级结构。乳腺CAFs中的表观遗传失调可能会提高乳腺癌细胞的存活率,并最终导致治疗耐药性。越来越多的证据表明,靶向组蛋白、DNA和miRNA的表观遗传调节剂是一种很有前景的癌症治疗方法。本综述旨在总结目前关于乳腺CAFs表观遗传调控机制的研究结果,并讨论通过靶向这些因素的潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41b0/7600259/937f7d651623/cancers-12-02949-g001.jpg

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