NF‐κB and epithelial to mesenchymal transition of cancer

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-kB family of transcription factors plays pivotal roles in both promoting and maintaining an invasive phenotype. After briefly describing the NF-kB family and its role in cancer, in this review we will first describe studies elucidating the functions of NF-kB in transcription of master regulator genes that repress an epithelial phenotype. In the second half, we discuss the roles of NF-kB in control of mesenchymal genes critical for promoting and maintaining an invasive phenotype. Overall, NF-kB is identified as a key target in prevention and in the treatment of invasive carcinomas.

Mechanisms of nitric oxide-mediated inhibition of EMT in cancer

“…[14][15][16] NFκB induces EMT via regulation of the expression of multiple matrix proteases, adhesion molecules and both angiogenic and invasive factors. 14,[17][18][19][20][21] In contrast, inhibition of NFκB by various means suppresses EMT and inhibits tumor cell metastasis.…”

“…[14][15][16] NFκB induces EMT via regulation of the expression of multiple matrix proteases, adhesion molecules and both angiogenic and invasive factors. 14,[17][18][19][20][21] In contrast, inhibition of NFκB by various means suppresses EMT and inhibits tumor cell metastasis. [18][19][20][21][22] Recently, NFκB was identified as a transcriptional activator of an additional EMT-inducer gene product, namely, Snail.…”

Keratin 8 and 18 Loss in Epithelial Cancer Cells Increases Collective Cell Migration and Cisplatin Sensitivity through Claudin1 Up-regulation

“…Pathway-Several studies have indicated that transcription factor NF-B activity is involved in both promoting and maintaining an invasive phenotype (40). Western blot analysis showed a 3.4-fold (Ϯ0.18; p Ͻ 0.0008) and a 3.1-fold increase (Ϯ0.07; p Ͻ 0.0011) of IB␣ phosphorylation in K8/18-depleted KLE and HepG2 cells, respectively (Fig.…”

Mouse Snail Is a Target Gene for HIF

“…Several signaling pathways regulating Snail transcription have been identified (3). Both mitogen-activated protein kinase (MAPK) and NFkB stimulate transcription through regions in the minimal promoter of Snail (9,10) and many signaling molecules implicated in EMT progression use both signaling pathways to mediate their response (10)(11)(12)(13)(14). Other signaling pathways implicated in EMT, including Wnt and phosphoinositide 3-kinase (15,16), use GSK-3 to mediate their responses.…”