| RRC ID |
51708
|
| 著者 |
Tarhan YE, Kato T, Jang M, Haga Y, Ueda K, Nakamura Y, Park JH.
|
| タイトル |
Morphological Changes, Cadherin Switching, and Growth Suppression in Pancreatic Cancer by GALNT6 Knockdown.
|
| ジャーナル |
Neoplasia
|
| 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.
|
| 巻・号 |
18(5)
|
| ページ |
265-272
|
| 公開日 |
2016-5-1
|
| DOI |
10.1016/j.neo.2016.03.005
|
| PII |
S1476-5586(16)30003-3
|
| PMID |
27237318
|
| PMC |
PMC4887616
|
| MeSH |
Cadherins / metabolism*
Cell Line, Tumor
Cell Survival / genetics
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Gene Silencing
Glycosylation
Humans
Mucin-4 / genetics
Mucin-4 / metabolism
N-Acetylgalactosaminyltransferases / deficiency*
N-Acetylgalactosaminyltransferases / genetics
Pancreatic Neoplasms / genetics*
Pancreatic Neoplasms / metabolism*
Pancreatic Neoplasms / pathology
RNA, Small Interfering / genetics
Signal Transduction
|
| IF |
5.696
|
| 引用数 |
20
|
| リソース情報 |
| ヒト・動物細胞 |
KP4(RCB1005) |
