Role of Receptor Sialylation in the Ovarian Tumor Cell Phenotype.

摘要

The overarching goal of our research is to define the role of a cancer-associated glycosyltransferase, ST6Gal-I, in regulating the ovarian tumor cell phenotype. In the first year of this pilot project, significant progress has been made toward establishing ST6Gal-I s function in protecting tumor cells from apoptosis. These results establish a new paradigm in apoptotic signaling, particularly given that there is a marked dearth of evidence concerning glycosylation-dependent mechanisms in tumor cell survival. We also show that tumor cells can be sensitized to cisplatin-induced cell death through forced downregulation of ST6Gal-I. Platin drugs represent a first-line treatment for ovarian cancer, therefore therapeutic targeting of ST6Gal-I may hold promise for treating patients that have become chemoresistant. Finally, preliminary results indicate that ST6Gal-I protein is upregulated in human ovarian tumors, implicating ST6Gal-I as a potential new biomarker. In the upcoming year, our studies will focus on elucidating the mechanistic basis by which ST6Gal-I modulates the activity of integrins and death receptors to control tumor cell invasion and apoptosis-resistance.