Epithelial mesenchymal transition (EMT) in prostate growth and tumor progression.
Epithelial mesenchymal transition (EMT) in prostate growth and tumor progression.
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DOI：
10.3978/j.issn.2223-4683.2013.09.04
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发表时间：
2013-09-01
影响因子：
2
通讯作者：
Kyprianou N
中科院分区：
文献类型：
--
作者：
Grant CM;Kyprianou N
上皮-间充质转化（Epithelial-mesenchymal transition， EMT）及其逆转，即间充质-上皮转化（mesenchymal-epithelial transition， MET），是干细胞发育和多能性调控过程中必不可少的形态学过程，但这些过程在病理环境中也被激活，如纤维化和癌症进展。多组分信号通路通过转录、转录后、翻译和翻译后调控，共同启动EMT和MET程序。EMT是组织再生和正常胚胎发育所必需的，因为它使上皮细胞获得间充质表型，赋予它们在原肠胚形成和器官形成过程中形成三维结构的迁移和动态特性。这种现象的不受控制的激活以及成人生活中EMT事件的信号通路，导致癌症生长，并通过微环境的信号相互作用进行协调，极性增强的上皮肿瘤细胞具有侵袭性并迅速转移到远处。实体瘤前沿上皮标记物（E-cadherin）的丢失和间充质标记物（N-cadherin）的获得与转移的进展有关。本文将探讨EMT对GU器官胚胎发育的贡献以及EMT- met周期在前列腺肿瘤发生中的功能影响。我们将讨论在前列腺癌发展为转移性去势抵抗疾病过程中驱动EMT及其逆转为MET的关键因素的最新见解，特别关注雄激素受体（AR）和转化生长因子-β (TGF-β)信号在前列腺癌进展中的预测和靶向价值。
Epithelial-mesenchymal transition (EMT) and its reversal, mesenchymal-epithelial transition (MET), are essential morphological processes during development and in the regulation of stem cell pluripotency, yet these processes are also activated in pathological contexts, such as in fibrosis and cancer progression. Multi-component signaling pathways cooperate in initiation of EMT and MET programs, via transcriptional, post-transcriptional, translational, and post-translational regulation. EMT is required for tissue regeneration and normal embryonic development as it enables epithelial cells to acquire the mesenchymal phenotype, conferring them migratory and dynamic properties towards forming three-dimensional structures during gastrulation and organ formation. Uncontrolled activation of such phenomenon and the pathways signaling EMT events in adult life, leads to cancer growth and orchestrated by signaling interactions from the microenvironment, epithelial tumor cells with enhanced polarity, become invasive and rapidly metastasize to distant sites. Loss of epithelial markers (E-cadherin) and gain of mesenchymal markers (N-cadherin), at the leading edge of solid tumors is associated with progression to metastasis. This review will explore the contribution of EMT to embryonic development of GU organs and the functional consequences of EMT-MET cycles in prostate tumorigenesis. Recent insights identifying key players driving EMT and its reversal to MET during prostate cancer progression to metastatic castration-resistant disease will be discussed, with specific focus on androgen receptor (AR) and transforming growth factor-β (TGF-β) signaling in the context of their predictive and targeting value in prostate cancer progression.