Dong Bo, Qiu Zhaoping, Wu Yadi
Department of Pharmacology and Nutritional Sciences, University of Kentucky School of Medicine, Lexington, KY, United States.
Markey Cancer Center, University of Kentucky School of Medicine, Lexington, KY, United States.
Front Pharmacol. 2020 Nov 27;11:596239. doi: 10.3389/fphar.2020.596239. eCollection 2020.
Epithelial-mesenchymal Transition (EMT) is a de-differentiation process in which epithelial cells lose their epithelial properties to acquire mesenchymal features. EMT is essential for embryogenesis and wound healing but is aberrantly activated in pathological conditions like fibrosis and cancer. Tumor-associated EMT contributes to cancer cell initiation, invasion, metastasis, drug resistance and recurrence. This dynamic and reversible event is governed by EMT-transcription factors (EMT-TFs) with epigenetic complexes. In this review, we discuss recent advances regarding the mechanisms that modulate EMT in the context of epigenetic regulation, with emphasis on epigenetic drugs, such as DNA demethylating reagents, inhibitors of histone modifiers and non-coding RNA medication. Therapeutic contributions that improve epigenetic regulation of EMT will translate the clinical manifestation as treating cancer progression more efficiently.
上皮-间质转化(EMT)是一种去分化过程,在此过程中上皮细胞丧失其上皮特性以获得间质特征。EMT对于胚胎发育和伤口愈合至关重要,但在诸如纤维化和癌症等病理条件下会被异常激活。肿瘤相关的EMT促进癌细胞的起始、侵袭、转移、耐药性和复发。这一动态且可逆的事件由具有表观遗传复合物的EMT转录因子(EMT-TFs)调控。在本综述中,我们讨论了在表观遗传调控背景下调节EMT的机制的最新进展,重点是表观遗传药物,如DNA去甲基化试剂、组蛋白修饰抑制剂和非编码RNA药物。改善EMT表观遗传调控的治疗作用将转化为更有效地治疗癌症进展的临床表现。