NF-kappaB and epithelial to mesenchymal transition of cancer.
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.
Min
Chengyin
C
Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118-2394, USA.
Eddy
Sean F
SF
Sherr
David H
DH
Sonenshein
Gail E
GE
D000818:Animals; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000473:pathology*; D010641:Phenotype; D014746:Vimentin / Q000378:metabolism
D016328:NF-kappa B; D014746:Vimentin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9