EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer.
EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer.
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EMT，癌症干细胞和耐药性：癌症战争中新兴的邪恶轴。
DOI：
10.1038/onc.2010.215
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发表时间：
2010-08-26
期刊：
影响因子：
8
通讯作者：
Settleman, J.
中科院分区：
文献类型：
--
作者：
Singh, A.;Settleman, J.
肿瘤在细胞和分子上是异质性的，未分化的癌细胞亚群表现出干细胞样特征(CSCs)。上皮向间充质转化(EMT)是胚胎发育过程中组织形态发生所必需的转分化过程。多种细胞因子和生长因子可以调节内胚层转移过程，如转化生长因子-β，它们的活性在肿瘤进展过程中被异常调节。因此，EMT在癌细胞中的诱导导致获得侵袭和转移特性。最近的报道表明，CSCs的出现部分是由于EMT的结果，例如，通过来自肿瘤间质成分的线索。最近的证据表明，肿瘤细胞的EMT不仅会导致转移增加，而且还会导致耐药。在这篇综述中，我们将为EMT诱导和CSCs的出现之间的联系提供潜在的机制解释。我们还将重点介绍最近的研究，涉及转化生长因子-β调控的非编码RNA在驱动EMT和促进CSC自我更新方面的功能。最后，我们将讨论EMT和CSCs如何导致耐药，以及临床上克服这种耐药的治疗策略。
Tumors are cellularly and moleculary heterogeneous, with subsets of undifferentiated cancer cells exhibiting stem cell-like features (CSCs). Epithelial to mesenchymal transitions (EMT) are transdifferentiation programs that are required for tissue morphogenesis during embryonic development. The EMT process can be regulated by a diverse array of cytokines and growth factors, such as TGF-β whose activities are dysregulated during malignant tumor progression. Thus, EMT induction in cancer cells results in the acquisition of invasive and metastatic properties. Recent reports indicate that the emergence of CSCs occurs in part as a result of EMT, for example, via cues from tumor stromal components. Recent evidence now indicates that EMT of tumor cells not only causes increased metastasis but also contributes to drug resistance. In this review, we will provide potential mechanistic explanations for the association between EMT induction and the emergence of CSCs. We will also highlight recent studies implicating the function of TGF-β regulated non-coding RNAs in driving EMT and promoting CSC self-renewal. Finally we will discuss how EMT and CSCs may contribute to drug resistance as well as therapeutic strategies to overcome this clinically.
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