Hyaluronic acid induces transglutaminase II to enhance cell motility; role of Rac1 and FAK in the induction of transglutaminase II.
The role of transglutaminase II (TGase II) in hyaluronic acid (HA)-promoted melanoma cell motility was investigated. HA induced the expression of TGase II via the nuclear factor kappaB (NF-kB) in melanoma cells. HA increased the Rac1 activity and phosphorylation of focal adhesion kinase (FAK). Transfection by lipofectamine of dominant-negative Rac1, and FAK-related non-kinase (FRNK), an endogenous inhibitor of FAK, suppressed the induction of TGase II. This suggests that Rac1 and FAK mediate induction of TGase II by HA. HA-promoted melanoma cell motility was inhibited by cystamine, an inhibitor of TGase II, and overexpression of TGase II enhanced melanoma cell motility through reactive oxygen species. Taken together, HA promotes melanoma cell motility through activation of Rac1, FAK, and induction of TGase II.
Kim
Youngmi
Y
School of Biological Sciences, College of Natural Sciences, Kangwon National University, Chunchon 200-701, Korea.
Park
Young Woo
YW
Lee
Yun-Sil
YS
Jeoung
Dooil
D
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D008545:Melanoma / Q000378:metabolism*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011503:Transglutaminases / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
C107953:RAC1 protein, human; D017382:Reactive Oxygen Species; D006820:Hyaluronic Acid; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019204:GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein