The Intimate Relationship Among EMT, MET and TME: A T(ransdifferentiation) E(nhancing) M(ix) to Be Exploited for Therapeutic Purposes.
The Intimate Relationship Among EMT, MET and TME: A T(ransdifferentiation) E(nhancing) M(ix) to Be Exploited for Therapeutic Purposes.
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DOI：
10.3390/cancers12123674
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发表时间：
2020-12-07
期刊：
影响因子：
5.2
通讯作者：
Ungefroren H
中科院分区：
文献类型：
--
作者：
Hass R;von der Ohe J;Ungefroren H
肿瘤内异质性被认为是癌症患者耐药性和治疗失败的主要原因。肿瘤细胞以其表型可塑性而闻名，即细胞重新编程并改变其身份以最终采用多种表型的能力。肿瘤细胞的可塑性涉及发育程序的重新激活、癌症干细胞特性的获得以及逆分化或转分化的增强潜力。众所周知的转分化机制是上皮-间充质转化（EMT）过程。目前的证据表明，EMT、遗传和表观遗传改变以及来自肿瘤微环境（TME）的各种信号在塑造肿瘤细胞的可塑性方面存在复杂的相互作用。当癌细胞处于可塑性或干细胞样状态时，其暴露的脆弱性有可能在治疗上被利用，即，通过将高转移性细胞转化为侵袭性较低甚至无害的有丝分裂后细胞。肿瘤内异质性被认为是癌症中药物无反应性的主要原因，并且越来越多的证据表明非突变耐药机制而不是其发展中的基因突变。这些非突变过程在很大程度上由表型可塑性驱动，表型可塑性被定义为细胞重新编程和改变其身份的能力（表型转换）。肿瘤细胞可塑性的特征在于与癌症干细胞特性的获得和增强的逆分化或转分化潜力密切相关的发育程序的重新激活。表型可塑性的一个充分研究的机制是上皮-间充质转化（EMT）。目前的证据表明，EMT、遗传和表观遗传改变以及来自细胞重编程中肿瘤微环境的线索之间存在复杂的相互作用。更深入地了解干细胞，上皮-间充质和肿瘤相关重编程事件之间的联系对于开发减轻细胞可塑性并最大限度地减少肿瘤异质性演变以及耐药性的新疗法至关重要。或者，可以在治疗上利用肿瘤细胞在处于可塑性或干细胞样状态时暴露的脆弱性，即，将它们转化为攻击性较低的甚至是有丝分裂后的细胞。因此，肿瘤细胞可塑性为理解癌症对治疗的抵抗力和破译其潜在机制提供了一个新的范例。
Intratumoral heterogeneity is considered the major cause of drug resistance and hence treatment failure in cancer patients. Tumor cells are known for their phenotypic plasticity that is the ability of a cell to reprogram and change its identity to eventually adopt multiple phenotypes. Tumor cell plasticity involves the reactivation of developmental programs, the acquisition of cancer stem cell properties and an enhanced potential for retro- or transdifferentiation. A well-known transdifferentiation mechanism is the process of epithelial-mesenchymal transition (EMT). Current evidence suggests a complex interplay between EMT, genetic and epigenetic alterations, and various signals from the tumor microenvironment (TME) in shaping a tumor cell’s plasticity. The vulnerabilities exposed by cancer cells when residing in a plastic or stem-like state have the potential to be exploited therapeutically, i.e., by converting highly metastatic cells into less aggressive or even harmless postmitotic ones. Intratumoral heterogeneity is considered the major cause of drug unresponsiveness in cancer and accumulating evidence implicates non-mutational resistance mechanisms rather than genetic mutations in its development. These non-mutational processes are largely driven by phenotypic plasticity, which is defined as the ability of a cell to reprogram and change its identity (phenotype switching). Tumor cell plasticity is characterized by the reactivation of developmental programs that are closely correlated with the acquisition of cancer stem cell properties and an enhanced potential for retrodifferentiation or transdifferentiation. A well-studied mechanism of phenotypic plasticity is the epithelial-mesenchymal transition (EMT). Current evidence suggests a complex interplay between EMT, genetic and epigenetic alterations, and clues from the tumor microenvironment in cell reprogramming. A deeper understanding of the connections between stem cell, epithelial–mesenchymal, and tumor-associated reprogramming events is crucial to develop novel therapies that mitigate cell plasticity and minimize the evolution of tumor heterogeneity, and hence drug resistance. Alternatively, vulnerabilities exposed by tumor cells when residing in a plastic or stem-like state may be exploited therapeutically, i.e., by converting them into less aggressive or even postmitotic cells. Tumor cell plasticity thus presents a new paradigm for understanding a cancer’s resistance to therapy and deciphering its underlying mechanisms.
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EMT亚型影响上皮可塑性和细胞迁移模式。
影响因子：
11.8
作者：
Aiello NM;Maddipati R;Norgard RJ;Balli D;Li J;Yuan S;Yamazoe T;Black T;Sahmoud A;Furth EE;Bar-Sagi D;Stanger BZ
通讯作者：
Stanger BZ
影响因子：
82.9
作者：
Beltran H;Prandi D;Mosquera JM;Benelli M;Puca L;Cyrta J;Marotz C;Giannopoulou E;Chakravarthi BV;Varambally S;Tomlins SA;Nanus DM;Tagawa ST;Van Allen EM;Elemento O;Sboner A;Garraway LA;Rubin MA;Demichelis F
通讯作者：
Demichelis F
影响因子：
14.5
作者：
da Silva-Diz, Victoria;Lorenzo-Sanz, Laura;Munoz, Purification
通讯作者：
Munoz, Purification
影响因子：
11.2
作者：
Casas E;Kim J;Bendesky A;Ohno-Machado L;Wolfe CJ;Yang J
通讯作者：
Yang J
影响因子：
15.9
作者：
Charytonowicz, Elizabeth;Terry, Melissa;Matushansky, Igor
通讯作者：
Matushansky, Igor