NF-κB: Its role in colorectal cancer

Abstract

Colorectal cancer (CRC) is a major worldwide health problem and is the second leading cause of cancer-related deaths in the United States. Despite considerable progress in diagnosis and treatment, a high mortality rate persists, largely due to the complications associated with metastatic incidences. The pro-inflammatory transcription factor nuclear factor κB (NF-κB) is a central player in inflammatory responses and tumor progression. In CRC, constitutively activated NF-κB has been observed in the majority of patients. NF-κB significantly affects the process of tumorigenesis by promoting many aspects including tumor growth, proliferation, invasiveness, and angiogenesis. Importantly, the critical contribution of NF-κB to inflammation and tumorigenesis is due to its control of the expression of a large variety of target genes, many of which, when aberrantly expressed, help to orchestrate and promote CRC malignant potential. These NF-κB target genes include those vital to cell cycle regulation, cell proliferation, metastasis, and cell survival. Additionally, activation of NF-κB in both cancerous cells and inflammatory cells and subsequent induction of cytokines/chemokines within the tumor microenvironment also contribute to CRC cell malignancy in both autocrine and paracrine manners. These evidences implicate inhibition of NF-κB as an important approach for CRC therapy. Several recent combinatorial approaches using classical chemotherapeutics with NF-κB inhibitors seem to have resulted in very promising outcomes.