The Glycoprotein Mucin-1 Negatively Regulates GalNAc Transferase 5 Expression in Pancreatic Cancer

Overview

Journal FEBS Lett

Specialty Biochemistry

Date 2019 Jul 9

PMID 31283009

Citations 10

Authors

Thomas Caffrey

Satish Sagar

Divya Thomas

Michelle E Lewallen

Michael A Hollingsworth

Prakash Radhakrishnan

Affiliations

Soon will be listed here.

Abstract

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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