| 抄録 |
目的: UDP-GalNAc: polypeptide N-acetylgalactosaminyl-transferases (GalNAc-Ts) GalNAc-Ts regulate the first committed step in mucin biosynthesis, determine sites of O-glycosylation on proteins, and are important for understanding normal and carcinoma-associated O-glycosylation. Of the GalNAc-transferases, we evaluate the role of GalNAc-T3 in pancreatic ductal adenocarcinoma (PDAC).方法: We examined the knockdown effects of GalNAc-T3 on cell growth using in vitro assays and in vivo tumor xenograft growth model in nude mice. To identify the substrates of GalNAc-T3, we identified differently expressed proteins in the membrane fractions of stable control and GalNAc-T3 RNAi PDAC cells by silver staining SDS-PAGE gels. The different bands were excised and analyzed by Q-TOF-MS after in-gel trypsin digestion. The functional analyses and identification of O-glycosylation of the candidate proteins were performed.結果: Suppression of GalNAc-T3 expression in PDAC cells by RNAi results in growth suppression of cancer cells in vitro and in vivo. We also report that GNAT1 may be a substrate protein of GalNAc-T3 and play a similarly important role in the viability of PDAC cells. It is likely that GalNAc-T3 acts on substrate proteins that are important for the growth and/or survival of PDAC cells, and contributes to cell growth/survival in an epigenetic manner based on their substrate specificities.まとめ: Our results imply that GalNAc-T3 contributes to the function of mucins and thereby affects the growth and survival of pancreatic cancer cells. Thus, substrate proteins of GalNAc-T3 should serve as important therapeutic targets for pancreatic cancers. |
