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Abstract

Constitutive activation of the EGFR is common in cancer due to EGFR wild-type (EGFRwt) overexpression or the presence of mutant EGFR. Signaling by constitutively active NSCLC EGFR mutants or the EGFRvIII mutant in glioblastoma has been studied intensively and the downstream signals are known. Normally, the EGFRwt is activated when it is exposed to ligand, resulting in activation of canonical signals such as ERK and Akt. The EGFRwt also becomes tyrosine phosphorylated and constitutively activated without ligand when it is overexpressed, but downstream signals are unclear. Recent studies have identified a noncanonical form of signaling triggered by EGFRwt exclusively in the absence of ligand that does not involve ERK or Akt activation but, instead, results in activation of the transcription factor IRF3. The addition of ligand turns off IRF3-dependent transcription and activates ERK and Akt. Thus, the EGFR triggers distinct and mutually exclusive signaling networks, depending on the presence of ligand. Furthermore, noncanonical EGFRwt signaling may influence response to treatment in cancer. Also, there are reports of both synergistic and antagonistic interactions between ligand-dependent EGFRwt and EGFRvIII signaling. Here, we discuss ligand-inde-pendent EGFR signal transduction by oncogenic EGFR mutants and EGFRwt, and review the interplay between EGFRwt and EGFRvIII.

Original languageEnglish (US)
Pages (from-to)3436-3441
Number of pages6
JournalCancer Research
Volume75
Issue number17
DOIs
StatePublished - Sep 1 2015

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Ligands
Glioblastoma
Tyrosine
Signal Transduction
Neoplasms
Transcription Factors
epidermal growth factor receptor VIII

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ligand-independent EGFR signaling. / Guo, Gao; Gong, Ke; Wohlfeld, Bryan; Hatanpaa, Kimmo J.; Zhao, Dawen; Habib, Amyn A.

In: Cancer Research, Vol. 75, No. 17, 01.09.2015, p. 3436-3441.

Research output: Contribution to journalArticle

Guo, Gao ; Gong, Ke ; Wohlfeld, Bryan ; Hatanpaa, Kimmo J. ; Zhao, Dawen ; Habib, Amyn A. / Ligand-independent EGFR signaling. In: Cancer Research. 2015 ; Vol. 75, No. 17. pp. 3436-3441.
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