UAP1 is overexpressed in prostate cancer and is protective against inhibitors of N -linked glycosylation

摘要: Prostate cancer is the second most common cause of cancer-associated deaths in men, and signaling via a transcription factor called androgen receptor (AR) an important driver disease. Consequently, AR target genes are prominent candidates to be specific for prostate also survival cells. Here we assess levels all hexosamine biosynthetic pathway (HBP) enzymes 15 separate clinical gene expression data sets identify last enzyme pathway, UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1), highly overexpressed cancer. We analyzed 3261 cancers on tissue microarray found that UAP1 staining correlates negatively with Gleason score (P=0.0039) positively high (P<0.0001). Cells have 10-fold increased HBP end-product, (UDP-GlcNAc). UDP-GlcNAc essential N-linked glycosylation occurring endoplasmic reticulum (ER) associates resistance against inhibitors (tunicamycin 2-deoxyglucose) but not general ER stress-inducing agent, calcium ionophore A23187. Knockdown re-sensitized cells towards glycosylation, as measured by proliferation activation stress markers. Taken together, identified enzyme, UAP1, which protects from conferring growth advantage.