Bornes Laura, Belthier Guillaume, van Rheenen Jacco
Oncode Institute, The Netherlands Cancer Institute, Division of Molecular Pathology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
J Clin Med. 2021 May 29;10(11):2403. doi: 10.3390/jcm10112403.
Epithelial-to-mesenchymal transition (EMT) is a cellular program which leads to cells losing epithelial features, including cell polarity, cell-cell adhesion and attachment to the basement membrane, while gaining mesenchymal characteristics, such as invasive properties and stemness. This program is involved in embryogenesis, wound healing and cancer progression. Over the years, the role of EMT in cancer progression has been heavily debated, and the requirement of this process in metastasis even has been disputed. In this review, we discuss previous discrepancies in the light of recent findings on EMT, plasticity and hybrid E/M states. Moreover, we highlight various tumor microenvironmental cues and cell intrinsic signaling pathways that induce and sustain EMT programs, plasticity and hybrid E/M states. Lastly, we discuss how recent findings on plasticity, especially on those that enable cells to switch between hybrid E/M states, have changed our understanding on the role of EMT in cancer metastasis, stemness and therapy resistance.
上皮-间质转化(EMT)是一个细胞程序,它导致细胞失去上皮特征,包括细胞极性、细胞间粘附和与基底膜的附着,同时获得间质特征,如侵袭性和干性。该程序参与胚胎发育、伤口愈合和癌症进展。多年来,EMT在癌症进展中的作用一直存在激烈争论,甚至该过程在转移中的必要性也备受争议。在本综述中,我们根据最近关于EMT、可塑性和混合E/M状态的研究结果,讨论先前存在的差异。此外,我们强调了诱导和维持EMT程序、可塑性和混合E/M状态的各种肿瘤微环境线索和细胞内在信号通路。最后,我们讨论了最近关于可塑性的研究结果,特别是那些使细胞能够在混合E/M状态之间转换的研究结果,如何改变了我们对EMT在癌症转移、干性和治疗抗性中作用的理解。