Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Int J Cancer. 2021 Jun 15;148(12):2884-2897. doi: 10.1002/ijc.33398. Epub 2020 Nov 30.
Cancerous tumours contain a rare subset of cells with stem-like properties that are termed cancer stem cells (CSCs). CSCs are defined by their ability to divide both symmetrically and asymmetrically, to initiate new tumour growth and to tolerate the foreign niches required for metastatic dissemination. Accumulating evidence suggests that tumours arise from cells with stem-like properties, the generation of CSCs is therefore likely to be an initiatory event in carcinogenesis. Furthermore, CSCs in established tumours exist in a dynamic and plastic state, with nonstem tumour cells thought to be capable of de-differentiation to CSCs. The regulation of the CSC state both during tumour initiation and within established tumours is a desirable therapeutic target and is mediated by epigenetic factors. In this review, we will explore the epigenetic parallels between induced pluripotency and the generation of CSCs, and discuss how the epigenetic regulation of CSCs opens up novel opportunities for therapeutic intervention.
癌细胞中包含一小部分具有干细胞特性的细胞，被称为癌症干细胞（CSC）。CSC 的定义是其具有对称和不对称分裂的能力，能够启动新的肿瘤生长，并耐受转移扩散所需的外来小生境。越来越多的证据表明，肿瘤是由具有干细胞特性的细胞产生的，因此 CSC 的产生很可能是癌变的起始事件。此外，在已建立的肿瘤中，CSC 处于动态和可塑性状态，非干细胞肿瘤细胞被认为能够去分化为 CSC。在肿瘤起始和已建立的肿瘤中调节 CSC 状态是一个理想的治疗靶点，并受表观遗传因素的调节。在这篇综述中，我们将探讨诱导多能性与 CSC 产生之间的表观遗传学相似性，并讨论 CSC 的表观遗传调控如何为治疗干预开辟新的机会。
