title: Morphological Changes, Cadherin Switching, and Growth Suppression in Pancreatic Cancer by GALNT6 Knockdown.
abstract: 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.
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yunus Emre
authors.initials: YE
authors.lastname: Tarhan
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Taigo
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Miran
authors.initials: M
authors.lastname: Jang
authors.affiliation: Cancer Proteomics Group, Genome Center, Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Haga
authors.affiliation: Cancer Proteomics Group, Genome Center, Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA; Department of Surgery, The University of Chicago, Chicago, IL 60637, USA. Electronic address: ynakamura@bsd.uchicago.edu.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Park
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006031:Glycosylation; D006801:Humans; D055264:Mucin-4 / Q000235:genetics / Q000378:metabolism; D017350:N-Acetylgalactosaminyltransferases / Q000172:deficiency* / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D015820:Cadherins; D055264:Mucin-4; D017350:N-Acetylgalactosaminyltransferases; D034741:RNA, Small Interfering; D000097763:Polypeptide N-acetylgalactosaminyltransferase