Identification of an exon 4-deletion variant of epidermal growth factor receptor with increased metastasis-promoting capacity

Neoplasia. 2011 May;13(5):461-71. doi: 10.1593/neo.101744.


Several types of epidermal growth factor receptor (EGFR) gene alternations have been observed in human tumors. Here we present a novel EGFR variant with aberrant splicing of exon 4 (named as de4 EGFR). Variant-specific polymerase chain reaction showed that de4 EGFR was expressed in some glioma (4/40), prostate cancer (3/11), and ovarian cancer (3/9) tissues but not in tissues adjacent to tumors or normal tissues. de4 EGFR displayed an enhanced transformation and a higher metastasis-promoting capacity in comparison to wild-type EGFR. With minimal EGF-binding activity, de4 EGFR underwent ligand-independent autophosphorylation and self-dimerization. Moreover, in serum-starved condition, de4 EGFR expression in U87 MG cells significantly upregulated the extracellular signal-regulated kinase and AKT phosphorylation and expression of JUN and Src. Importantly, E-cadherin expression was barely detectable in the U87 MG cells expressing de4 EGFR and restored expression of E-cadherin in these cells inhibited their metastatic behaviors. Taken together, we identified a novel EGFR variant with increased metastasis-promoting activity that may become a promising new target for cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytoma
  • Base Sequence
  • Cadherins / biosynthesis
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Line
  • Cell Proliferation
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism*
  • Exons
  • Extracellular Signal-Regulated MAP Kinases / biosynthesis
  • Female
  • Genes, src
  • Glioblastoma
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Male
  • Mice
  • Neoplasm Metastasis
  • Oncogene Protein p65(gag-jun) / metabolism
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Phosphorylation
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Sequence Deletion*


  • Cadherins
  • Oncogene Protein p65(gag-jun)
  • ErbB Receptors
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases