The role of epithelial-mesenchymal transition programming in invasion and metastasis: a clinical perspective.
The role of epithelial-mesenchymal transition programming in invasion and metastasis: a clinical perspective.
复制标题
DOI：
10.2147/cmar.s35171
复制
发表时间：
2013-01-01
影响因子：
3.3
通讯作者：
Kurie, Jonathan M
中科院分区：
文献类型：
--
作者：
Creighton, Chad J;Gibbons, Don L;Kurie, Jonathan M
上皮间充质转化（Epithelial-mesenchymal transition， EMT）参与正常的细胞发育过程，但它也可能被一部分癌细胞所利用，使它们能够在远处侵入并形成转移灶。几种基因转录因子调控EMT，包括Snail1、Snail2、Zeb1、Zeb2和Twist；正在进行的研究继续确定和阐明其他驱动因素。特定的微核糖核酸（rna）也被发现可以调节EMT，包括靶向Zeb1/Zeb2的microRNA-200 （miR-200）家族。癌症“干细胞”——具有自我更新和再生肿瘤内所有细胞类型的能力——已被发现表达EMT标记，进一步暗示癌症干细胞和EMT都与转移有关。微环境线索，包括转化生长因子- β，可以通过调节miR-200的表达来指导EMT肿瘤转移。在人类肿瘤中，EMT标记物和调节因子可能在肿瘤细胞的一个亚群中表达，例如在侵袭前沿或肿瘤-微环境界面的细胞中表达，尽管某些亚型的癌症可以表现出广泛的间充质样特征。在EMT患者的治疗靶向方面，潜在的探索领域可能包括靶向癌症干细胞亚群，以及重新引入miR-200的基于microrna的治疗方法。这篇综述将探讨EMT在肿瘤侵袭和转移中的作用，重点是肺癌和乳腺癌的研究。我们还对公开可用的基因表达谱数据集进行了分析，以显示emt相关基因如何在人类肿瘤标本中协调表达。
Epithelial-mesenchymal transition (EMT) is involved in normal developmental cellular processes, but it may also be co-opted by a subset of cancer cells, to enable them to invade and form metastases at distant sites. Several gene transcription factors regulate EMT, including Snail1, Snail2, Zeb1, Zeb2, and Twist; ongoing studies continue to identify and elucidate other drivers. Specific micro ribonucleic acids (RNAs) have also been found to regulate EMT, including the microRNA-200 (miR-200) family, which targets Zeb1/Zeb2. Cancer "stem cells" - with the ability to self-renew and to regenerate all the cell types within the tumor - have been found to express EMT markers, further implicating both cancer stem cells and EMT with metastasis. Microenvironmental cues, including transforming growth factor-beta, can direct EMT tumor metastasis, such as by regulating miR-200 expression. In human tumors, EMT markers and regulators may be expressed in a subset of tumor cells, such as in cells at the invasive front or tumor-microenvironment interface, though certain subtypes of cancer can show widespread mesenchymal-like features. In terms of therapeutic targeting of EMT in patients, potential areas of exploration could include targeting the cancer stem cell subpopulation, as well as microRNA-based therapeutics that reintroduce miR-200. This review will examine evidence for a role of EMT in invasion and metastasis, with the focus being on studies in lung and breast cancers. We also carry out analyses of publicly-available gene expression profiling datasets in order to show how EMT-associated genes appear coordinately expressed across human tumor specimens.