Interplay of the iron-regulated metastasis suppressor NDRG1 with epidermal growth factor receptor (EGFR) and oncogenic signaling

J Biol Chem. 2017 Aug 4;292(31):12772-12782. doi: 10.1074/jbc.R117.776393. Epub 2017 Jun 14.

Abstract

The iron-regulated metastasis suppressor N-myc downstream-regulated gene 1 (NDRG1) has been shown to inhibit numerous oncogenic signaling pathways in cancer cells. Recent findings have demonstrated that NDRG1 inhibits the ErbB family of receptors, which function as key inducers of carcinogenesis. NDRG1 attenuates ErbB signaling by inhibiting formation of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) and HER2/HER3 heterodimers and by down-regulating EGFR via a mechanism involving its degradation. Understanding the complex interplay between NDRG1, iron, and ErbB signaling is vital for identifying novel, more effective targets for cancer therapy.

Keywords: NDRG1; cancer therapy; cell signaling; epidermal growth factor receptor (EGFR); iron; metastasis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Carcinogenesis*
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism*
  • Clathrin-Coated Vesicles
  • Endocytosis
  • Endosomes / enzymology
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / chemistry
  • ErbB Receptors / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Iron / metabolism
  • Ligands
  • Models, Biological*
  • Protein Multimerization
  • Proteolysis
  • Receptor, ErbB-2 / agonists
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / chemistry
  • Receptor, ErbB-2 / metabolism
  • Receptor, ErbB-3 / agonists
  • Receptor, ErbB-3 / antagonists & inhibitors*
  • Receptor, ErbB-3 / chemistry
  • Receptor, ErbB-3 / metabolism
  • Receptors, Transferrin / agonists
  • Receptors, Transferrin / metabolism
  • Signal Transduction*
  • Transferrin / metabolism

Substances

  • Antigens, CD
  • CD71 antigen
  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • N-myc downstream-regulated gene 1 protein
  • Receptors, Transferrin
  • Transferrin
  • Iron
  • EGFR protein, human
  • ERBB2 protein, human
  • ERBB3 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • Receptor, ErbB-3