Betaig-h3 interacts with alpha3beta1 integrin to promote adhesion and migration of human hepatoma cells.
betaig-h3 is a TGF-induced extracellular matrix (ECM) protein. Our previous evidence suggests that beta ig-h3 may promote adhesion and invasion potential of human hepatoma cells, but the mechanism underlying this process is still unknown. The present study identifies a pivotal role for molecules of the beta ig-h3 signal transduction pathway. We demonstrated that beta ig-h3 co-immunoprecipitated with alpha 3beta 1 integrin in human 7721 hepatoma cells. The addition of alpha 3beta 1 integrin antibodies inhibited the elevated adhesion and migration in beta ig-h3-over-expressing 7721 cells, but not in beta ig-h3 siRNA transfected 7721 cells. The expression and activity of integrin downstream molecules FAK and paxillin show a positive correlation with beta ig-h3 expression in different human hepatoma cells. Levels of focal adhesions and stress fibers were decreased in beta ig-h3 siRNA transfected 7721 cells. We suggest that by interaction with alpha 3beta 1 integrin, beta ig-h3 activates FAK-paxillin signaling linkage, leads to cytoskeleton reorganization, and thus enhances the metastatic potentials of human hepatoma cells.
Tang
Juan
J
Cell Engineering Research Centre and Department of Cell Biology, State Key Laboratory of Cancer Biology, the Fourth Military Medical University, 17 West Changle Road, Xi'an 710032, China.
Wu
Ya-Mei
YM
Zhao
Pu
P
Jiang
Jian-Li
JL
Chen
Zhi-Nan
ZN
D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000503:physiopathology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D003599:Cytoskeleton / Q000473:pathology / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D039201:Integrin alpha3beta1 / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000473:pathology / Q000503:physiopathology; D009361:Neoplasm Invasiveness; D051419:Paxillin / Q000235:genetics; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D000099222:betaIG-H3 Protein
D016326:Extracellular Matrix Proteins; D051417:Focal Adhesion Kinase 1; D039201:Integrin alpha3beta1; D051419:Paxillin; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C496050:PTK2 protein, human