Vascular endothelial growth factor (VEGF) enhances gastric carcinoma invasiveness via integrin alpha(v)beta6.
Integrins play an important role in tumor metastasis induced by vascular endothelial growth factor (VEGF). However, in the case of gastric cancer, the precise role of VEGF in regulating integrin alphavbeta6 is unclear. In this study, we found that most of the alphavbeta6 integrin-positive gastric cancer tissues were also VEGF-positive. Furthermore, when gastric carcinoma cells were exposed to VEGF, expression of alphavbeta6 integrin was up-regulated and the extracellular signal-related kinase (ERK) pathway was activated. When integrin alphavbeta6 was blocked either with beta6 siRNA or anti-alphavbeta6 antibody, the migration of tumor cells normally induced by VEGF, as well as the activation of ERK, were markedly inhibited. Blocking the ERK signaling pathway significantly inhibited cell mobility. Taken together, the data suggest that VEGF is critical to the invasive process in human gastric cancer and that this occurs via up-regulation of integrin alphavbeta6 expression and activation of ERK.
Zhao
Rui
R
Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, PR China.
Liu
Xiang-qun
XQ
Wu
Xiao-peng
XP
Liu
Yan-feng
YF
Zhang
Zhao-yang
ZY
Yang
Guang-yun
GY
Guo
Sen
S
Niu
Jun
J
Wang
Jia-yong
JY
Xu
Ke-sen
KS
D000906:Antibodies; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002070:Butadienes / Q000494:pharmacology; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009570:Nitriles / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D000906:Antibodies; D000951:Antigens, Neoplasm; D002070:Butadienes; D016023:Integrins; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D011994:Recombinant Proteins; C113580:U 0126; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C073878:integrin alphavbeta6; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9