NF-κB: Its Role in Colorectal Cancer

Chapter

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.

Keywords

Colorectal cancer NF-κB Transcription factor 

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Copyright information

© Springer Nature Singapore Pte Ltd 2017

Authors and Affiliations

  • A. Hartley
    • 1
  • H. Wei
    • 1
  • L. Prabhu
    • 1
  • M. Martin
    • 1
  • T. Lu
    • 1
    • 2
    • 3
  1. 1.Department of Pharmacology and ToxicologyIndiana University School of MedicineIndianapolisUSA
  2. 2.Department of Biochemistry and Molecular BiologyIndiana University School of MedicineIndianapolisUSA
  3. 3.Department of Medical and Molecular GeneticsIndiana University School of MedicineIndianapolisUSA

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