Epithelial-Mesenchymal Transition (EMT) and Prostate Cancer
Epithelial-Mesenchymal Transition (EMT) and Prostate Cancer
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DOI：
10.1007/978-3-319-95693-0_6
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发表时间：
2018-01-01
期刊：
影响因子：
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通讯作者：
Sweeney, Janae
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文献类型：
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作者：
Odero-Marah, Valerie;Hawsawi, Ohuod;Sweeney, Janae
通常情况下，正常的上皮细胞是一层单层，被粘着的蛋白质紧紧地抓住，阻止细胞从单层膜上动员。在前列腺癌的发展过程中，上皮细胞可以经历上皮-间充质转化或EMT，其特征是其表型从立方体转变为纺锤形。这与生化变化有关，其中上皮细胞标志物如E-钙粘蛋白和阻滞素下调，导致细胞与细胞之间的黏附丧失，而间充质标志物如波形蛋白和N-钙粘附素上调，从而允许细胞迁移或转移到不同的器官。包括生长因子和细胞因子，如转化生长因子-β、表皮生长因子和胰岛素样生长因子，以及丝裂原活化蛋白激酶和磷脂酰肌醇3-激酶等信号通路，可直接或间接调节EMT的转变。该信号随后诱导多种转录因子的表达，如Snail、Twist、ZEB1/2，这些转录因子也被称为EMT的主要调节因子。在前列腺癌患者组织中已经报道了与EMT相关的各种标志物，以及可能与健康差异有关的因素。人们一直在考虑通过靶向EMT信号通路来治疗前列腺癌患者的EMT。
Typically the normal epithelial cells are a single layer, held tightly by adherent proteins that prevent the mobilization of the cells from the monolayer sheet. During prostate cancer progression, the epithelial cells can undergo epithelial- mesenchymal transition or EMT, characterized by morphological changes in their phenotype from cuboidal to spindle-shaped. This is associated with biochemical changes in which epithelial cell markers such as E-cadherin and occludins are down-regulated, which leads to loss of cell-cell adhesion, while mesenchymal markers such as vimentin and N-cadherin are up-regulated, thereby allowing the cells to migrate or metastasize to different organs. The EMT transition can be regulated directly and indirectly by multiple molecular mechanisms including growth factors and cytokines such as transforming growth factor-beta (TGF-beta), epidermal growth factor (EGF) and insulin-like growth factor (IGF), and signaling pathways such as mitogen-activated protein kinase (MAPK) and Phosphatidylinositol 3-Kinase (PI3K). This signaling subsequently induces expression of various transcription factors like Snail, Twist, Zeb1/2, that are also known as master regulators of EMT. Various markers associated with EMT have been reported in prostate cancer patient tissue as well as a possible association with health disparities. There has been consideration to therapeutically target EMT in prostate cancer patients by targeting the EMT signaling pathways.