The effect of epidermal growth factor receptor variant III on glioma cell migration by stimulating ERK phosphorylation through the focal adhesion kinase signaling pathway.
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.
Liu
Mingzhu
M
Department of Biochemistry and Molecular Biology, Fudan University, Shanghai, PR China.
Yang
Yong
Y
Wang
Can
C
Sun
Lidong
L
Mei
Chuanzhong
C
Yao
Wantong
W
Liu
Yonglei
Y
Shi
Yinghong
Y
Qiu
Shuangjian
S
Fan
Jia
J
Cai
Xiumei
X
Zha
Xiliang
X
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
D013925:Thromboplastin; D066246:ErbB Receptors; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases