Discovery proteomics defines androgen-regulated glycoprotein networks in prostate cancer cells, as well as putative biomarkers of prostatic diseases

Jordy J Hsiao; Melinda M Smits; Brandon H Ng; Jinhee Lee; Michael E Wright

doi:10.1038/s41598-021-01554-2

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Discovery proteomics defines androgen-regulated glycoprotein networks in prostate cancer cells, as well as putative biomarkers of prostatic diseases

Journal article

Open access

Peer reviewed

Discovery proteomics defines androgen-regulated glycoprotein networks in prostate cancer cells, as well as putative biomarkers of prostatic diseases

Jordy J Hsiao, Melinda M Smits, Brandon H Ng, Jinhee Lee and Michael E Wright

Scientific reports, Vol.11(1), pp.22208-22208

11/15/2021

DOI: 10.1038/s41598-021-01554-2

PMCID: PMC8592995

PMID: 34782677

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Abstract

Supraphysiologic androgen (SPA) inhibits cell proliferation in prostate cancer (PCa) cells by transcriptional repression of DNA replication and cell-cycle genes. In this study, quantitative glycoprotein profiling identified androgen-regulated glycoprotein networks associated with SPA-mediated inhibition of PCa cell proliferation, and androgen-regulated glycoproteins in clinical prostate tissues. SPA-regulated glycoprotein networks were enriched for translation factors and ribosomal proteins, proteins that are known to be O-GlcNAcylated in response to various cellular stresses. Thus, androgen-regulated glycoproteins are likely to be targeted for O-GlcNAcylation. Comparative analysis of glycosylated proteins in PCa cells and clinical prostate tissue identified androgen-regulated glycoproteins that are differentially expressed prostate tissues at various stages of cancer. Notably, the enzyme ectonucleoside triphosphate diphosphohydrolase 5 was found to be an androgen-regulated glycoprotein in PCa cells, with higher expression in cancerous versus non-cancerous prostate tissue. Our glycoproteomics study provides an experimental framework for characterizing androgen-regulated proteins and glycoprotein networks, toward better understanding how this subproteome leads to physiologic and supraphysiologic proliferation responses in PCa cells, and their potential use as druggable biomarkers of dysregulated AR-dependent signaling in PCa cells.

Androgens - metabolism

Biomarkers

Cell Line, Tumor

Computational Biology - methods

Gene Expression Regulation, Neoplastic

Glycoproteins - genetics

Glycoproteins - metabolism

Humans

Male

Mass Spectrometry

Prostatic Diseases - etiology

Prostatic Diseases - metabolism

Prostatic Neoplasms - etiology

Prostatic Neoplasms - metabolism

Proteome

Proteomics - methods

Signal Transduction

Details

Title: Subtitle: Discovery proteomics defines androgen-regulated glycoprotein networks in prostate cancer cells, as well as putative biomarkers of prostatic diseases
Creators: Jordy J Hsiao - Roy J. and Lucille A. Carver College of Medicine
Melinda M Smits - Roy J. and Lucille A. Carver College of Medicine
Brandon H Ng - Roy J. and Lucille A. Carver College of Medicine
Jinhee Lee - University of Iowa
Michael E Wright - Roy J. and Lucille A. Carver College of Medicine
Resource Type: Journal article
Publication Details: Scientific reports, Vol.11(1), pp.22208-22208
DOI: 10.1038/s41598-021-01554-2
PMID: 34782677
PMCID: PMC8592995
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Grant note: W81XWH-08-1-0471 / U.S. Department of Defense
Language: English
Date published: 11/15/2021
Academic Unit: Molecular Physiology and Biophysics
Record Identifier: 9984297605602771

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