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EGFR wild type antagonizes EGFRvIII-mediated activation of Met in glioblastoma.

Abstract
Epidermal growth factor receptor (EGFR)vIII is the most common EGFR mutant found in glioblastoma (GBM). EGFRvIII does not bind ligand, is highly oncogenic and is usually coexpressed with EGFR wild type (EGFRwt). EGFRvIII activates Met, and Met contributes to EGFRvIII-mediated oncogenicity and resistance to treatment. Here, we report that addition of EGF results in a rapid loss of EGFRvIII-driven Met phosphorylation in glioma cells. Met is associated with EGFRvIII in a physical complex. Addition of EGF results in a dissociation of the EGFRvIII-Met complex with a concomitant loss of Met phosphorylation. Consistent with the abrogation of Met activation, addition of EGF results in the inhibition of EGFRvIII-mediated resistance to chemotherapy. Thus, our study suggests that ligand in the milieu of EGFRvIII-expressing GBM cells is likely to influence the EGFRvIII-Met interaction and resistance to treatment, and highlights a novel antagonistic interaction between EGFRwt and EGFRvIII in glioma cells.
AuthorsL Li, V T Puliyappadamba, S Chakraborty, A Rehman, V Vemireddy, D Saha, R F Souza, K J Hatanpaa, P Koduru, S Burma, D A Boothman, A A Habib
JournalOncogene (Oncogene) Vol. 34 Issue 1 Pg. 129-134 (Jan 02 2015) ISSN: 1476-5594 [Electronic] England
PMID24362532 (Publication Type: Journal Article)
Chemical References
  • epidermal growth factor receptor VIII
  • Epidermal Growth Factor
  • Dacarbazine
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins c-met
  • Receptor Protein-Tyrosine Kinases
  • Temozolomide
Topics
  • Brain Neoplasms (drug therapy, metabolism)
  • Cell Line, Tumor
  • Dacarbazine (analogs & derivatives, chemistry)
  • Epidermal Growth Factor (metabolism)
  • ErbB Receptors (metabolism)
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma (drug therapy, metabolism)
  • Humans
  • Phenotype
  • Phosphorylation
  • Proto-Oncogene Proteins c-met (metabolism)
  • Receptor Protein-Tyrosine Kinases (antagonists & inhibitors)
  • Temozolomide

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