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

doi:10.1002/1873-3468.13532

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 journal › Article › peer-review

12 Scopus citations

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 language	English (US)
Pages (from-to)	2751-2761
Number of pages	11
Journal	FEBS Letters
Volume	593
Issue number	19
DOIs	https://doi.org/10.1002/1873-3468.13532
State	Published - Oct 1 2019

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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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",

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AU - Caffrey, Thomas

AU - Sagar, Satish

AU - Thomas, Divya

AU - Lewallen, Michelle E.

AU - Hollingsworth, Michael A.

AU - Radhakrishnan, Prakash

PY - 2019/10/1

Y1 - 2019/10/1

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

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

Abstract

Keywords

ASJC Scopus subject areas

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