title: Caveolin-1 up-regulates ST6Gal-I to promote the adhesive capability of mouse hepatocarcinoma cells to fibronectin via FAK-mediated adhesion signaling.
abstract: Caveolin-1 is a major structural protein of caveolae and plays important functions in tumorigenesis and development. Hca-F and Hepa1-6 are mouse hepatocarcinoma cell lines with high and low malignant potential, respectively. Our previous studies revealed that caveolin-1 promoted cell invasion by up-regulating the glycosylation of matrix metalloproteinase inducer CD147 of Hepa1-6 and Hca-F cells. However, the roles of caveolin-1 in cell-ECM adhesion and the mechanisms involved remain unknown. This study showed that caveolin-1 overexpression in Hepa1-6 cells up-regulated sialyltransferase ST6Gal-I expression and activated FAK-mediated adhesion signaling, and down-regulation of ST6Gal-I attenuated caveolin-1-induced increase in the adhesive ability of Hepa1-6 cells to fibronectin. Conversely, caveolin-1 knockdown in Hca-F cells inhibited ST6Gal-I expression and FAK signaling-mediated cell adhesion to fibronectin. Re-expression of wild-type caveolin-1 or ST6Gal-I rescued the decreased ST6Gal-I expression and adhesion of Hca-F cells caused by caveolin-1 silencing. Further studies indicated that caveolin-1 might regulate ST6Gal-I expression through caveolin-1 scaffolding domain. Taken together, these results demonstrate for the first time that caveolin-1 can up-regulate ST6Gal-I expression and further contribute to promoting mouse hepatocarcinoma cell adhesion to fibronectin by activating FAK-mediated adhesion signaling.
authors.affiliation: Department of Biochemistry, Institute of Glycobiology, Dalian Medical University, Dalian 116044, Liaoning Province, China.
authors.forename: Shengjin
authors.initials: S
authors.lastname: Yu
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.forename: Nanyang
authors.initials: N
authors.lastname: Li
authors.forename: Jianhui
authors.initials: J
authors.lastname: Fan
authors.forename: Linhua
authors.initials: L
authors.lastname: Liu
authors.forename: Jianing
authors.initials: J
authors.lastname: Zhang
authors.forename: Shujing
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D012799:Sialyltransferases / Q000096:biosynthesis*; D015398:Signal Transduction; D015854:Up-Regulation; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D051242:Caveolin 1; D005353:Fibronectins; D012799:Sialyltransferases; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase