Morphological Changes, Cadherin Switching, and Growth Suppression in Pancreatic Cancer by GALNT6 Knockdown

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• 作者：Yunus Emre Tarhan^* ; Taigo Kato^* ; Miran Jang^* ; Yoshimi Haga^&Dagger ; ; Koji Ueda^&Dagger ; ; Yusuke Nakamura^* ; ^&dagger ; ; ^{ynakamura@bsd.uchicago.edu" class="auth_mail" title="E-mail the corresponding author} ; Jae-Hyun Park^*
• 刊名：Neoplasia
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：18
• 期：5
• 页码：265-272
• 全文大小：1294 K

文摘

Pancreatic cancer reveals the worst prognosis among human cancers with little improvement in its clinical outcome in the last three decades. We previously suggested that polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6), which catalyzes O-type glycosylation of Mucin 1, might be a promising molecular target for drug development for breast cancer. In this study, we report upregulation of GALNT6 in pancreatic cancer cells where Mucin proteins are highly O-glycosylated. We found that knockdown of GALNT6 with small interfering RNA in pancreatic cancer cells decreased the amount of Mucin 4 protein as well as that of its transcript, reduced the levels of human epidermal growth factor receptor 2 and extracellular signal–regulated kinase, and significantly reduced pancreatic cancer cell viability. Interestingly, knockdown of GALNT6 caused drastic morphological changes of pancreatic cells, accompanied with the cadherin switching from P-cadherin to E-cadherin. Considering important roles of Mucin 4 in growth and invasion, our findings imply that targeting GALNT6 is a very promising therapeutic strategy for treatment of pancreatic cancer patients who still have very limited treatment modalities.