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.