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Focus on HER4

HER4 is part of the complex network of HER signaling pathways

HER4 is part of the complex network of HER signaling pathways
HER4 is a part of the highly complex signaling network of the HER family receptors. HER4 and its effects in cancer are not as well characterized as are HER1/EGFR, HER2, and HER3. The prognostic role of HER4 is poorly understood.1-3 Adapted with permission from Lippincott Williams & Wilkins. Sliwkowski MX. In: Harris JR, Lippman ME, Morrow M, Osborne CK, eds. Diseases of the Breast. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2004:415-426.

Although HER4 signaling in normal cells has been well characterized, its activity in cancer is poorly understood.

Biochemistry of HER4


  • HER4, like HER1/EGFR, contains both a ligand-binding domain and a tyrosine kinase domain2
  • HER4 ligands include heregulin, the neuregulins, betacellulin, and epiregulin4,5
  • In normal breast tissue, HER4 may be involved in breast tissue differentiation as well as lactation1,6

Does HER4 play a role in cancer?


  • On the surface of breast and ovarian cancer cells, HER4 is present in much smaller quantities than other HER family receptors7
    • Thus, HER4 may not be as available as other HER family receptors for dimerization and signaling pathway initiation
  • One preclinical study (Campiglio et al, 1999) suggests that HER3/HER4 heterodimers may be responsible for prolonged activation of mitogen-associated protein kinase (MAPK), which leads to cellular proliferation5
  • Additional preclinical work by Feng et al in 2007 associates HER4 with cell growth inhibition rather than with proliferation6

The value of HER4 as a prognostic factor is being investigated


  • Few studies have examined the relationship between HER4 and prognosis. However, unlike other HER pathway receptors, HER4 has been reported to be associated with improved, rather than poorer, prognosis2,3
  • Further research is needed to better characterize the role of HER4 in tumor biology. This receptor appears to be less important to the development of cancer than other members of the HER family

 

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