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EMT: Mechanisms and therapeutic implications
Pharmacology & Therapeutics ( IF 13.5 ) Pub Date : 2017-08-20 , DOI: 10.1016/j.pharmthera.2017.08.009
Mohini Singh , Nicolas Yelle , Chitra Venugopal , Sheila K. Singh

Metastasis, the dissemination of cancer cells from primary tumors, represents a major hurdle in the treatment of cancer. The epithelial-mesenchymal transition (EMT) has been studied in normal mammalian development for decades, and it has been proposed as a critical mechanism during cancer progression and metastasis. EMT is tightly regulated by several internal and external cues that orchestrate the shifting from an epithelial-like phenotype into a mesenchymal phenotype, relying on a delicate balance between these two stages to promote metastatic development. EMT is thought to be induced in a subset of metastatic cancer stem cells (MCSCs), bestowing this population with the ability to spread throughout the body and contributing to therapy resistance. The EMT pathway is of increasing interest as a novel therapeutic avenue in the treatment of cancer, and could be targeted to prevent tumor cell dissemination in early stage patients or to eradicate existing metastatic cells in advanced stages. In this review, we describe the sequence of events and defining mechanisms that take place during EMT, and how these interactions drive cancer cell progression into metastasis. We summarize clinical interventions focused on targeting various aspects of EMT and their contribution to preventing cancer dissemination.



中文翻译:

EMT:机制和治疗意义

转移,即从原发性肿瘤中扩散癌细胞,代表了癌症治疗的主要障碍。上皮-间质转化(EMT)已经在哺乳动物的正常发育中进行了数十年的研究,并且被认为是癌症进展和转移过程中的关键机制。EMT受到几种内部和外部线索的严格调节,这些线索可以协调从上皮样表型向间充质表型的转变,这依赖于这两个阶段之间的微妙平衡来促进转移性发展。人们认为EMT是在转移性癌症干细胞(MCSC)的子集中诱导的,这使该人群具有在整个人体中扩散的能力并有助于治疗抵抗力。作为治疗癌症的新型治疗途径,EMT途径受到越来越多的关注,并有可能在早期阶段阻止肿瘤细胞的扩散或在晚期根除已有的转移细胞。在这篇综述中,我们描述了事件序列和在EMT期间发生的定义机制,以及这些相互作用如何驱动癌细胞发展为转移。我们总结了针对EMT各个方面的临床干预措施及其对预防癌症传播的作用。

更新日期:2017-08-20
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