表观遗传学与肿瘤干细胞

Epigenetics in cancer stem cells

肿瘤干细胞模型是关于肿瘤形成及生物学特征的一种重要观点。该模型认为肿瘤发生的核心是一群类似于成体干细胞的肿瘤细胞,具有自我增殖和分化潜能,称为肿瘤干细胞(Cancer stem cells,CSCs)。目前在多种肿瘤中都发现了CSCs,其不仅能导致肿瘤发生,还是引起肿瘤转移、复发、抗药的关键原因。因此,研究CSC的调控机制具有重要意义。近年来的研究发现,除了基础的遗传学因素外,表观遗传学在CSCs的调控中同样具有重要作用。目前主要的表观遗传学机制包括DNA甲基化、组蛋白修饰、染色质重塑及miRNA等,能有效调节基因表达及细胞表型,也是肿瘤研究的新热点。文章主要围绕近几年CSCs的特性研究及表观遗传学线索,阐述表观遗传学机制调控CSCs的最新进展。

According to the types of stem cells and considering tumor evolution, one of the most significant theories about stem cells is derived from cancer stem cells （CSCs）, which, similar to normal adult stem cells, possess the capacity of self-renewal and potential of differentiation. Over the past few years, compelling evidence has emerged in support of the CSC model for many tumors. The CSCs are posited to be responsible not only for tumor initiation but also for tumor metastasis, relapse and therapyresistance. Thus, understanding the mechanisms that govern the generation and maintenance of this special population of cells is of great importance. Despite the current progress in basic genetic research, the latest work implies that epigenetic mechanisms, from DNA methylation, histone modifications and chromatin-remodeling to the wide discovered miRNAs, play critical roles in the regulation of CSC features. This review focuses on the key epigenetic mechanisms that regulate and define the unique CSC properties.