title: Identification of an exon 4-deletion variant of epidermal growth factor receptor with increased metastasis-promoting capacity.
abstract: 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.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Cancer Institute.
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.forename: Bizhi
authors.initials: B
authors.lastname: Shi
authors.forename: Qingli
authors.initials: Q
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Sun
authors.forename: Jianhua
authors.initials: J
authors.lastname: Liu
authors.forename: Keke
authors.initials: K
authors.lastname: Zhou
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.forename: Jianren
authors.initials: J
authors.lastname: Gu
authors.forename: Shengli
authors.initials: S
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
authors.forename: Zonghai
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D001254:Astrocytoma; D001483:Base Sequence; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D005091:Exons; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis; D005260:Female; D016391:Genes, src; D005909:Glioblastoma; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D016759:Oncogene Protein p65(gag-jun) / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017384:Sequence Deletion
chemical_list: D015820:Cadherins; D016759:Oncogene Protein p65(gag-jun); D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases