期刊
FEBS LETTERS
卷 593, 期 19, 页码 2751-2761出版社
WILEY
DOI: 10.1002/1873-3468.13532
关键词
GalNAc-T5; glycosyltransferase; MUC1-CT; pancreatic cancer
资金
- National Insitutes of Health [R01 CA208108, P50CA127297, 5U01CA111294, 5U01CA210240, U54 CA163120, NE-DHHS/LB506]
Aberrant expression of the glycoprotein mucin-1 (MUC1) has been associated with pancreatic cancer progression and metastasis as a result of mediating the oncogenic transcriptional regulation of target genes. In the present study, we demonstrate that MUC1 downregulates the expression of the tumor suppressor polypeptide N-acetylgalactosaminyltransferase 5 in pancreatic cancer. ChIP-on-chip analysis revealed that the MUC1 cytoplasmic tail binds to regulatory elements in the GALNT5 gene. Additionally, MUC1 increases binding of p53 and c-Jun and decreases the binding of Sp1 to the proximal promoter and exonic regions of GALNT5. We also observed that expression of N-acetylgalactosaminyltransferase 5 is inversionally proportional to MUC1 expression in human pancreatic cancer. These results demonstrate that MUC1 downregulates the expression of N-acetylgalactosaminyltransferase 5 in pancreatic cancer by modifying the promoter occupancy of transcription factors through its cytoplasmic domain.
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