Mirzadeh Azad Fatemeh, Atlasi Yaser
Department of Life Sciences and Systems Biology, University of Turin, 10123 Turin, Italy.
Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast BT9 7AE, UK.
Cancers (Basel). 2021 Jul 14;13(14):3532. doi: 10.3390/cancers13143532.
Epigenetic regulations can shape a cell's identity by reversible modifications of the chromatin that ultimately control gene expression in response to internal and external cues. In this review, we first discuss the concept of cell plasticity in cancer, a process that is directly controlled by epigenetic mechanisms, with a particular focus on transcriptional enhancers as the cornerstone of epigenetic regulation. In the second part, we discuss mechanisms of enhancer deregulation in adult stem cells and epithelial-to-mesenchymal transition (EMT), as two paradigms of cell plasticity that are dependent on epigenetic regulation and serve as major sources of tumour heterogeneity. Finally, we review how genetic variations at enhancers and their epigenetic modifiers contribute to tumourigenesis, and we highlight examples of cancer drugs that target epigenetic modifications at enhancers.
表观遗传调控可通过对染色质进行可逆修饰来塑造细胞身份,这些修饰最终响应内部和外部信号控制基因表达。在本综述中,我们首先讨论癌症中细胞可塑性的概念,这一过程直接受表观遗传机制控制,特别关注转录增强子作为表观遗传调控的基石。在第二部分,我们讨论成体干细胞和上皮-间质转化(EMT)中增强子失调的机制,这两种细胞可塑性范式依赖于表观遗传调控,是肿瘤异质性的主要来源。最后,我们综述增强子及其表观遗传修饰因子的遗传变异如何促进肿瘤发生,并重点介绍靶向增强子表观遗传修饰的癌症药物实例。