EGFR and NF-κB: partners in cancer

Trends Mol Med. 2015 Jun;21(6):385-93. doi: 10.1016/j.molmed.2015.04.001. Epub 2015 May 13.

Abstract

Oncogenic proteins cooperate to promote tumor development and progression by sustaining cell proliferation, survival and invasiveness. Constitutive epidermal growth factor receptor (EGFR) and nuclear factor κb (NF-κB) activities are seen in multiple solid tumors and combine to provide oncogenic signals to cancer cells. Understanding how these oncogenic pathways are connected is crucial, given their role in intrinsic or acquired resistance to targeted anticancer therapies. We review molecular mechanisms by which both EGFR- and NF-κB-dependent pathways establish positive loops to increase their oncogenic potential. We also describe how NF-κB promotes resistance to EGFR inhibitors.

Keywords: EGFR; NF-κB; erlotinib; gefitinib; resistance; tumor-initiating cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drug Resistance, Neoplasm
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / immunology*
  • Erlotinib Hydrochloride / pharmacology
  • Erlotinib Hydrochloride / therapeutic use
  • Gefitinib
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyaluronoglucosaminidase
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / immunology*
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Proteins / immunology
  • Quinazolines / pharmacology
  • Quinazolines / therapeutic use
  • Signal Transduction* / drug effects

Substances

  • NF-kappa B
  • Protein Kinase Inhibitors
  • Proteins
  • Quinazolines
  • Erlotinib Hydrochloride
  • ErbB Receptors
  • CEMIP protein, human
  • Hyaluronoglucosaminidase
  • Gefitinib