The androgen receptor controls expression of the cancer-associated sTn antigen and cell adhesion through induction of ST6GalNAc1 in prostate cancer

摘要: Patterns of glycosylation are important in cancer, but the molecular mechanisms that drive changes often poorly understood. The androgen receptor drives prostate cancer (PCa) development and progression to lethal metastatic castration-resistant disease. Here we used RNA-Seq coupled with bioinformatic analyses androgen-receptor (AR) binding sites clinical PCa expression array data identify ST6GalNAc1 as a direct rapidly activated target gene AR cells. encodes sialytransferase catalyses formation cancer-associated sialyl-Tn antigen (sTn), which find is also induced by exposure. Androgens induce novel splice variant protein This shorter isoform still fully functional sialyltransferase able sTn-antigen. Surprisingly, given its high tumours, stable cells reduced tumours mice, cell adhesion switch towards more mesenchymal-like phenotype vitro. has dynamic pattern datasets, beingsignificantly up-regulated primary carcinoma relatively down-regulated established tissue. frequently upregulated concurrently another enzyme GCNT1 previously associated implicated Sialyl Lewis X synthesis. Together our establishes an androgen-dependent mechanism for sTn PCa, consistent general role driving coordinate glycoproteome during progression.