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)
Pages (from-to)2751-2761
Number of pages11
JournalFEBS Letters
Volume593
Issue number19
DOIs
StatePublished - Oct 1 2019

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Keywords

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

ASJC Scopus subject areas

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

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