Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences Old Road, University of Oxford, Oxford, OX3 7LD, UK.
Guangzhou Regenerative Medicine and Health Guangdong Laboratory, CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical University, Guangzhou, 510530, China.
Protein Cell. 2021 Jun;12(6):440-454. doi: 10.1007/s13238-020-00819-2. Epub 2021 Jan 16.
Dedifferentiation of cell identity to a progenitor-like or stem cell-like state with increased cellular plasticity is frequently observed in cancer formation. During this process, a subpopulation of cells in tumours acquires a stem cell-like state partially resembling to naturally occurring pluripotent stem cells that are temporarily present during early embryogenesis. Such characteristics allow these cancer stem cells (CSCs) to give rise to the whole tumour with its entire cellular heterogeneity and thereby support metastases formation while being resistant to current cancer therapeutics. Cancer development and progression are demarcated by transcriptional dysregulation. In this article, we explore the epigenetic mechanisms shaping gene expression during tumorigenesis and cancer stem cell formation, with an emphasis on 3D chromatin architecture. Comparing the pluripotent stem cell state and epigenetic reprogramming to dedifferentiation in cellular transformation provides intriguing insight to chromatin dynamics. We suggest that the 3D chromatin architecture could be used as a target for re-sensitizing cancer stem cells to therapeutics.
细胞身份去分化为祖细胞样或干细胞样状态，同时增加细胞可塑性，这种现象在癌症形成中经常观察到。在这个过程中，肿瘤中的一个细胞亚群获得了类似于自然发生的多能干细胞的干细胞样状态，这些多能干细胞在早期胚胎发生时暂时存在。这些特性使这些癌症干细胞（CSC）能够产生具有整个细胞异质性的整个肿瘤，并支持转移形成，同时对当前的癌症治疗具有抗性。癌症的发展和进展是由转录失调来划定的。在本文中，我们探讨了在肿瘤发生和癌症干细胞形成过程中塑造基因表达的表观遗传机制，重点是 3D 染色质结构。将多能干细胞状态和表观遗传重编程与细胞转化中的去分化进行比较，为染色质动力学提供了有趣的见解。我们认为，3D 染色质结构可以作为重新使癌症干细胞对治疗敏感的靶点。
