EGF receptor trafficking: consequences for signaling and cancer

Trends Cell Biol. 2014 Jan;24(1):26-34. doi: 10.1016/j.tcb.2013.11.002. Epub 2013 Nov 29.


The ligand-stimulated epidermal growth factor receptor (EGFR) has been extensively studied in the analysis of molecular mechanisms regulating endocytic traffic and the role of that traffic in signal transduction. Although such studies have largely focused on mitogenic signaling and dysregulated traffic in tumorigenesis, there is growing interest in the potential role of EGFR traffic in cell survival and the consequent response to cancer therapy. Here we review recent advances in our understanding of molecular mechanisms regulating ligand-stimulated EGFR activation, internalization, and post-endocytic sorting. The role of EGFR overexpression/mutation and new modulators of EGFR traffic in cancer and the response to cancer therapeutics are also discussed. Finally, we speculate on the relationship between EGFR traffic and cell survival.

Keywords: antineoplastic therapy; endocytosis; epidermal growth factor receptor (EGFR); oncogenes; trafficking; ubiquitination.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Endocytosis
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • GRB2 Adaptor Protein / metabolism
  • Humans
  • Multivesicular Bodies / metabolism
  • Mutation
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Protein Transport
  • Proteolysis
  • Signal Transduction*
  • Ubiquitination


  • Antineoplastic Agents
  • GRB2 Adaptor Protein
  • GRB2 protein, human
  • ErbB Receptors