The glycoprotein mucin-1 negatively regulates GalNAc transferase 5 expression in pancreatic cancer

Thomas Caffrey, Satish Sagar, Divya Thomas, Michelle E. Lewallen, Michael A Hollingsworth, Prakash Radhakrishnan

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalFEBS Letters
DOIs
StatePublished - Jan 1 2019

Fingerprint

Mucin-1
Pancreatic Neoplasms
Glycoproteins
N-Acetylgalactosaminyltransferases
Down-Regulation
Genes
Genetic Promoter Regions
polypeptide N-acetylgalactosaminyltransferase
Tail
Tumors
Transcription Factors
Neoplasm Metastasis
Neoplasms

Keywords

  • GalNAc-T5
  • MUC1-CT
  • glycosyltransferase
  • pancreatic cancer

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

The glycoprotein mucin-1 negatively regulates GalNAc transferase 5 expression in pancreatic cancer. / Caffrey, Thomas; Sagar, Satish; Thomas, Divya; Lewallen, Michelle E.; Hollingsworth, Michael A; Radhakrishnan, Prakash.

In: FEBS Letters, 01.01.2019.

Research output: Contribution to journalArticle

@article{1699d7f9fa274d459dc4ee402df6c2fc,
title = "The glycoprotein mucin-1 negatively regulates GalNAc transferase 5 expression in pancreatic cancer",
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.",
keywords = "GalNAc-T5, MUC1-CT, glycosyltransferase, pancreatic cancer",
author = "Thomas Caffrey and Satish Sagar and Divya Thomas and Lewallen, {Michelle E.} and Hollingsworth, {Michael A} and Prakash Radhakrishnan",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/1873-3468.13532",
language = "English (US)",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "Elsevier",

}

TY - JOUR

T1 - The glycoprotein mucin-1 negatively regulates GalNAc transferase 5 expression in pancreatic cancer

AU - Caffrey, Thomas

AU - Sagar, Satish

AU - Thomas, Divya

AU - Lewallen, Michelle E.

AU - Hollingsworth, Michael A

AU - Radhakrishnan, Prakash

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - GalNAc-T5

KW - MUC1-CT

KW - glycosyltransferase

KW - pancreatic cancer

UR - http://www.scopus.com/inward/record.url?scp=85069923676&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069923676&partnerID=8YFLogxK

U2 - 10.1002/1873-3468.13532

DO - 10.1002/1873-3468.13532

M3 - Article

JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

ER -