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: 3.37). 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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    • "RANKL-Induced Cellular Transformation Requires NF-kB and Wnt/b-Catenin Signaling Pathways As both the NF-kB and the Wnt/b-catenin signaling pathways are known to induce the EMT transcription factor Slug (Min et al., 2008; Zhou et al., 2004), we examined their role in RANKL-mediated cell transformation. Epithelial cells derived from FAC were treated with RANKL in the presence of pharmacological inhibitors specific to each of these signaling pathways, and examined for the RANKL-induced expression of vimentin and b-catenin (Figure 3A and Figure S3C). "
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    Cell host & microbe 11/2012; 12(5):645-56. DOI:10.1016/j.chom.2012.10.009 · 12.19 Impact Factor
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    • "Recent studies also show that NF-jB plays a critical role in tissue invasion, cell migration and metastasis. Importantly, NFjB has been identified as an important regulator of the EMT in many cancer cell types [19] [20] [21] [22]. The EMT has been shown to play a major role in invasion and metastasis of epithelial tumors. "
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    Cancer letters 08/2012; 334. DOI:10.1016/j.canlet.2012.08.003 · 5.62 Impact Factor
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    • "Growing evidence indicates that NF-kB plays a central role in EMT and metastasis by affecting the expression of mesenchymal genes (Huber et al., 2004; Min et al., 2008). In epithelial cells, a pool of the NF-kB p65 subunit (p65NF-kB) associates with Ecadherin and other cell-adhesion components. "
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    ABSTRACT: Snail1 is a transcriptional repressor of E-cadherin that triggers epithelial-mesenchymal transition (EMT). Here, we report assisted Snail1 interaction with the promoter of a typical mesenchymal gene, fibronectin (FN1), both in epithelial cells undergoing EMT and in fibroblasts. Together with Snail1, the p65 subunit of NF-κB and PARP1 bound to the FN1 promoter. We detected nuclear interaction of these proteins and demonstrated the requirement of all three for FN1 transcription. Moreover, other genes involved in cell movement mimic FN1 expression induced by Snail1 or TGF-β1 treatment and recruit p65NF-κB and Snail1 to their promoters. The molecular cooperation between Snail1 and NF-κB in transcription activation provides a new insight into how Snail1 can modulate a variety of cell programs.
    Journal of Cell Science 12/2011; 124(Pt 24):4161-71. DOI:10.1242/jcs.078824 · 5.33 Impact Factor
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