Whitehead Institute for Biomedical Research, Cambridge, MA, USA.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nat Rev Cancer. 2021 May;21(5):325-338. doi: 10.1038/s41568-021-00332-6. Epub 2021 Feb 5.
Epithelial stem cells serve critical physiological functions in the generation, maintenance and repair of diverse tissues through their ability to self-renew and spawn more specialized, differentiated cell types. In an analogous fashion, cancer stem cells have been proposed to fuel the growth, progression and recurrence of many carcinomas. Activation of an epithelial-mesenchymal transition (EMT), a latent cell-biological programme involved in development and wound healing, has been linked to the formation of both normal and neoplastic stem cells, but the mechanistic basis underlying this connection remains unclear. In this Perspective, we outline the instances where aspects of an EMT have been implicated in normal and neoplastic epithelial stem cells and consider the involvement of this programme during tissue regeneration and repair. We also discuss emerging concepts and evidence related to the heterogeneous and plastic cell states generated by EMT programmes and how these bear on our understanding of cancer stem cell biology and cancer metastasis. A more comprehensive accounting of the still-elusive links between EMT programmes and the stem cell state will surely advance our understanding of both normal stem cell biology and cancer pathogenesis.
上皮干细胞通过自我更新和产生更多特化、分化的细胞类型，在多种组织的生成、维持和修复中发挥关键的生理功能。类似地，癌症干细胞被认为是推动许多癌的生长、进展和复发的动力。上皮-间充质转化 (EMT) 的激活，这是一种参与发育和伤口愈合的潜在细胞生物学程序，与正常和肿瘤干细胞的形成有关，但这种联系的机制基础尚不清楚。在本观点中，我们概述了 EMT 的某些方面如何被牵涉到正常和肿瘤上皮干细胞中，并考虑了该程序在组织再生和修复中的参与。我们还讨论了 EMT 程序产生的异质和可塑性细胞状态的新兴概念和证据，以及这些概念如何影响我们对癌症干细胞生物学和癌症转移的理解。更全面地了解 EMT 程序与干细胞状态之间仍然难以捉摸的联系，肯定会增进我们对正常干细胞生物学和癌症发病机制的理解。
