Current Cancer Drug Targets

Ruiwen Zhang 
Texas Tech University Health Sciences Center
1300 Coulter Drive
Amarillo, TX 79106
USA

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Unveiling the Role of Nuclear Transport in Epithelial-to-Mesenchymal Transition

Author(s): Asfar S. Azmi.

Abstract:

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/β-Catenin, TGF-β, 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-β, 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.

Keywords: CRM1, EMT, Epithelial-to-mesenchymal transition, Exportin, Importin, Karyopherin, Nuclear Transport, Xpo1.

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Article Details

VOLUME: 13
ISSUE: 9
Year: 2013
Page: [906 - 914]
Pages: 9
DOI: 10.2174/15680096113136660096