title: The effect of epidermal growth factor receptor variant III on glioma cell migration by stimulating ERK phosphorylation through the focal adhesion kinase signaling pathway.
abstract: Epidermal growth factor receptor variant III (EGFRvIII), the most common EGFR mutation, is associated with cell migration of glioblastoma multiforme (GBM) cases; however, the mechanism has not been elucidated. In this study, we found that the EGFRvIII-promoted glioma cell migration was closely linked to high levels of tyrosine phosphorylation in focal adhesion kinase (FAK) Y397. We also demonstrated that EGFRvIII formed a complex with FAK, resulting in enhanced tyrosine phosphorylation levels of FAK Y397 and EGFR Y1068. After knockdown of FAK expression via anti-FAK shRNA, the U87ΔEGFR cell migration was significantly inhibited, accompanying with the reduced phosphorylation levels of extracellular signal-regulated kinase (ERK1/2). Furthermore, the role of ERK1/2 in FAK-regulated cell migration was confirmed. Taken together, our results suggest that FAK and its downstream molecule ERK were involved in EGFRvIII-promoted glioma cell migration in U87ΔEGFR cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Fudan University, Shanghai, PR China.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Liu
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Can
authors.initials: C
authors.lastname: Wang
authors.forename: Lidong
authors.initials: L
authors.lastname: Sun
authors.forename: Chuanzhong
authors.initials: C
authors.lastname: Mei
authors.forename: Wantong
authors.initials: W
authors.lastname: Yao
authors.forename: Yonglei
authors.initials: Y
authors.lastname: Liu
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Shi
authors.forename: Shuangjian
authors.initials: S
authors.lastname: Qiu
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.forename: Xiumei
authors.initials: X
authors.lastname: Cai
authors.forename: Xiliang
authors.initials: X
authors.lastname: Zha
mesh_terms: D002465:Cell Movement / Q000187:drug effects; D004817:Epidermis / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism; D005910:Glioma / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology*; D013925:Thromboplastin / Q000378:metabolism / Q000494:pharmacology
chemical_list: D013925:Thromboplastin; D066246:ErbB Receptors; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases