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The Under-Appreciated Promiscuity of the Epidermal Growth Factor Receptor Family

Sean P Kennedy1, Jordan F Hastings2, Jeremy Z R Han2

  • 1Systems Biology Ireland, University College DublinDublin, Ireland; Kinghorn Cancer Centre, Garvan Institute of Medical ResearchSydney, NSW, Australia.

Frontiers in Cell and Developmental Biology
|September 7, 2016
PubMed

Insights

Epidermal growth factor receptor (EGFR) family members form unexpected pairings beyond known dimers. This receptor promiscuity impacts targeted cancer therapy effectiveness and resistance mechanisms.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Epidermal growth factor receptor (EGFR) family members are crucial in development, homeostasis, and cancer.
  • Current understanding suggests EGFRs (EGFR, ERBB2, ERBB3, ERBB4) function primarily through homodimers and heterodimers within the family.
  • Receptor interactions influence signaling, localization, and function, and are implicated in resistance to targeted therapies.

Purpose of the Study:

  • To challenge the prevailing dogma of EGFR family receptor interactions.
  • To explore the potential for EGFR family receptors to interact with distantly related receptor tyrosine kinases (RTKs).
  • To discuss the implications of unexpected receptor pairings for targeted cancer therapy.

Main Methods:

  • Review and synthesis of existing scientific literature.
  • Discussion of experimental evidence challenging current models.
  • Analysis of the functional consequences of novel receptor interactions.

Main Results:

  • Evidence suggests EGFR family receptors can form unexpected pairings with other RTKs.
  • This promiscuity expands the potential interactome beyond established homodimers and heterodimers.
  • These novel interactions may significantly alter signaling pathways and cellular responses.

Conclusions:

  • The prevailing model of EGFR family signaling may be incomplete.
  • Receptor promiscuity offers new explanations for therapeutic resistance.
  • Understanding these unexpected pairings is critical for developing more effective targeted cancer therapies.
Keywords:
EGFRERBB2ERBB3ERBB4cancerheterodimerisationreceptor tyrosine kinasetherapeutic resistance

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