Article

NF-kappaB and epithelial to mesenchymal transition of cancer [J]

Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118-2394, USA.
Journal of Cellular Biochemistry (Impact Factor: 3.26). 06/2008; 104(3):733-44. DOI: 10.1002/jcb.21695
Source: PubMed

ABSTRACT

During progression of an in situ to an invasive cancer, epithelial cells lose expression of proteins that promote cell-cell contact, and acquire mesenchymal markers, which promote cell migration and invasion. These events bear extensive similarities to the process of epithelial to mesenchymal transition (EMT), which has been recognized for several decades as critical feature of embryogenesis. The NF-kappaB family of transcription factors plays pivotal roles in both promoting and maintaining an invasive phenotype. After briefly describing the NF-kappaB family and its role in cancer, in this review we will first describe studies elucidating the functions of NF-kappaB in transcription of master regulator genes that repress an epithelial phenotype. In the second half, we discuss the roles of NF-kappaB in control of mesenchymal genes critical for promoting and maintaining an invasive phenotype. Overall, NF-kappaB is identified as a key target in prevention and in the treatment of invasive carcinomas.

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Available from: David H Sherr, Sep 30, 2014
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    • "However, it remains to be studied. The transcription factor NFκB regulates the expression of several proteins that mediate the EMT process, such as Snail1/ 2, Twist1/2, ZEB1, vimentin, MMP-9, and MT1-MMP, which induces MMP-2 activation[34]. MMPs are involved in the EMT process because elevated levels of MMPs are able to induce EMT in the tumor microenvironment, whereas EMT process itself promotes MMP secretion. Moreover, MMPs are able to generate activated stroma-like cells that promote cancer progression[35,36]. "
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    • "MnSOD may also contribute to the genetic program of EMT by producing H 2 O 2 . This ROS is able to activate NF-κB, which plays a central role in the genetic program of EMT, by inducing directly or indirectly the expression of a family of zinc finger transcription factors, including Snail, Slug, Twist, and Zeb1 and Zeb2123124125. These actors are typical of EMT because they repress epithelial gene expression, as the best-studied cases, E-cadherin and γ-catenin, promote the loss of epithelial cell adhesion and polarity [116]. "
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    • "The induction of EMT can be triggered by transcription factors such as Snail, Slug, and Twist, which simultaneously repress the expression of genes that are required for the epithelial phenotype and induce the expression of genes required for mesenchymal properties [10]. The expression of these transcription factors is modulated by a number of signaling molecules, including nuclear factor kappa B (NF-κB) [10], [11]. NF-κB is a dimeric transcription factor composed of members of the Rel family, including RelA (p65) [12], [13]. "
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