NF-κB Signaling Pathway, Inflammation and Colorectal Cancer

There is growing evidence for a connection between inflammation and tumor development, and the nuclear factor kappa B (NF-kappa B), a proinflammatory transcription factor, is hypothesized to promote tumorigenesis. Although the genetic evidence for the hypothesis has been lacking, recent papers have lent credence to this hypothesis. It has been reported that constitutive NF-kappa B activation in inflammatory bowel diseases (IBDs) increases risk of colorectal cancer (CRC) in the patients with the number of years of active disease. NF-kappa B activation might induce cellular transformation, mediate cellular proliferation, prevent the elimination of pre-neoplastic and fully malignant cells by up-regulating the anti-apoptosis proteins. Furthermore, NF-kappa B may contribute to the progression of CRC by regulating the expression of diverse target genes that are involved in cell proliferation (Cyclin D1), angiogenesis (VEGF, IL-8, COX2), and metastasis (MMP9). These findings implicate NF-kappa B inhibition as an important therapeutic target in CRC. However, due to lack of knowledge about the specific roles of different NF-kappa B subunits in different stage of carcinogenesis, and compounds to block specific subunits of NF-kappa B family, it will be a long time before the coming of targeting NF-kappa B in CRC therapy. Cellular & Molecular Immunology. 2009;6(5):327-334.