Unveiling the Role of Nuclear Transport in Epithelial-to-Mesenchymal Transition
Unveiling the Role of Nuclear Transport in Epithelial-to-Mesenchymal Transition
复制标题
DOI：
10.2174/15680096113136660096
复制
发表时间：
2013-11-01
影响因子：
3
通讯作者：
Azmi, Asfar S.
中科院分区：
文献类型：
--
作者：
Azmi, Asfar S.
上皮间质转化（EMT）是一种现象，其中癌细胞失去极性，经历从上皮到间质的形态变化，从而实现可塑性，从而赋予侵袭和转移行为。 EMT过程涉及大量信号分子（Wnt/β-Catenin、TGF-β、Notch、EGF、HGF和缺氧）。 EMT 信号分子位于细胞外、细胞质或细胞核中。 Wnt、TGF-β、notch、EGF 和 HGF 信号传导从细胞表面的受体开始，通过细胞质，最终到达细胞核，其中信号传导级联导致 EMT 基因的表达。无论来源是什么，这些信号传导途径中每一种的最终效应分子都需要到达细胞核，以序列特异性方式在 DNA 上进行比对，并启动 EMT 促进基因的转录。从本质上讲，细胞运输，特别是由称为核传递蛋白的特殊蛋白质调节的核运输，在某种程度上直接或间接控制着大多数 EMT 促进途径。然而，目前还没有尝试了解在癌症中经常异常表达的核转运机制的改变对 EMT 发展的影响。这篇综述对核转运蛋白（导入蛋白和导出蛋白）在 EMT 发展中的作用提出了重要问题，并深入了解了未被充分认识的基于细胞转运的 EMT 信号分子调节，并讨论了靶向核导入和导出蛋白来控制 EMT 的可能性。
Epithelial-to-Mesenchymal transition (EMT) is a phenomenon in which cancer cells loose their polarity, undergo morphological changes from epithelial to mesenchymal thereby achieving plasticity that confers an invasive and metastatic behavior. A large number of signaling molecules (Wnt/beta-Catenin, TGF-beta, notch, EGF, HGF and hypoxia) have been implicated in the EMT process. The EMT signaling molecules are localized either extracellularly, in the cytosol, or in the nucleus. The Wnt, TGF-beta, notch, EGF and HGF signaling initiates from receptors on the cell surface through the cytoplasm and ultimately to the cell's nucleus where the signaling cascade leads to the expression of EMT genes. No matter what the source is, the ultimate effector molecules from each one of these signaling pathways need to reach cell nucleus, aligning on DNA in a sequence specific manner and initiating the transcription of EMT promoting genes. In essence cellular transport, particularly the nuclear transport that is regulated by specialized proteins called Karyopherins, in a way controls the majority of EMT promoting pathways either directly or indirectly. Nevertheless, there have been no attempts to understand the consequence of alterations in the nuclear transport machinery that is often times aberrantly expressed in cancer, on EMT development. This review poses important questions on the role of nuclear transporters (Importins and Exportins) in the development of EMT and provides an in depth understanding of the underappreciated cellular transport based regulation of EMT signaling molecules and also discusses the possibility of targeting the nuclear import and export proteins to rein in EMT.