Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, 6205, Bangladesh.
School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, QLD, 4029, Australia.
Stem Cell Rev Rep. 2020 Apr;16(2):397-412. doi: 10.1007/s12015-019-09942-y.
In embryonic development and throughout life, there are some cells can exhibit phenotypic plasticity. Phenotypic plasticity is the ability of cells to differentiate into multiple lineages. In normal development, plasticity is highly regulated whereas cancer cells re-activate this dynamic ability for their own progression. The re-activation of these mechanisms enables cancer cells to acquire a cancer stem cell (CSC) phenotype- a subpopulation of cells with increased ability to survive in a hostile environment and resist therapeutic insults. There are several contributors fuel CSC plasticity in different stages of disease progression such as a complex network of tumour stroma, epidermal microenvironment and different sub-compartments within tumour. These factors play a key role in the transformation of tumour cells from a stable condition to a progressive state. In addition, flexibility in the metabolic state of CSCs helps in disease progression. Moreover, epigenetic changes such as chromatin, DNA methylation could stimulate the phenotypic change of CSCs. Development of resistance to therapy due to highly plastic behaviour of CSCs is a major cause of treatment failure in cancers. However, recent studies explored that plasticity can also expose the weaknesses in CSCs, thereby could be utilized for future therapeutic development. Therefore, in this review, we discuss how cancer cells acquire the plasticity, especially the role of the normal developmental process, tumour microenvironment, and epigenetic changes in the development of plasticity. We further highlight the therapeutic resistance property of CSCs attributed by plasticity. Also, outline some potential therapeutic options against plasticity of CSCs. Graphical Abstract .
在胚胎发育和整个生命过程中，有些细胞可以表现出表型可塑性。表型可塑性是细胞分化为多个谱系的能力。在正常发育中，可塑性受到高度调控，而癌细胞重新激活这种动态能力以促进自身进展。这些机制的重新激活使癌细胞获得癌症干细胞（CSC）表型——一群具有更高能力在恶劣环境中存活和抵抗治疗损伤的细胞亚群。有几个因素在疾病进展的不同阶段促进 CSC 的可塑性，如肿瘤基质的复杂网络、表皮微环境以及肿瘤内的不同亚区。这些因素在肿瘤细胞从稳定状态向进行性状态的转化中起着关键作用。此外，CSC 代谢状态的灵活性有助于疾病的进展。此外，表观遗传变化，如染色质、DNA 甲基化，可以刺激 CSCs 的表型变化。CSC 高度可塑性导致的耐药性发展是癌症治疗失败的主要原因。然而，最近的研究表明，可塑性也可以暴露出 CSCs 的弱点，从而可以为未来的治疗发展提供依据。因此，在这篇综述中，我们讨论了癌细胞如何获得可塑性，特别是正常发育过程、肿瘤微环境和表观遗传变化在可塑性发展中的作用。我们进一步强调了 CSCs 可塑性导致的治疗抵抗特性。还概述了一些针对 CSCs 可塑性的潜在治疗选择。
