Cargando…

N-Glycoproteins Have a Major Role in MGL Binding to Colorectal Cancer Cell Lines: Associations with Overall Proteome Diversity

Colorectal cancer (CRC) is the second-leading cause of cancer death worldwide due in part to a high proportion of patients diagnosed at advanced stages of the disease. For this reason, many efforts have been made towards new approaches for early detection and prognosis. Cancer-associated aberrant gl...

Descripción completa

Detalles Bibliográficos
Autores principales: Pirro, Martina, Mohammed, Yassene, van Vliet, Sandra J., Rombouts, Yoann, Sciacca, Agnese, de Ru, Arnoud H., Janssen, George M. C., Tjokrodirijo, Rayman T. N., Wuhrer, Manfred, van Veelen, Peter A., Hensbergen, Paul J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432225/
https://www.ncbi.nlm.nih.gov/pubmed/32752259
http://dx.doi.org/10.3390/ijms21155522
_version_ 1783571750717489152
author Pirro, Martina
Mohammed, Yassene
van Vliet, Sandra J.
Rombouts, Yoann
Sciacca, Agnese
de Ru, Arnoud H.
Janssen, George M. C.
Tjokrodirijo, Rayman T. N.
Wuhrer, Manfred
van Veelen, Peter A.
Hensbergen, Paul J.
author_facet Pirro, Martina
Mohammed, Yassene
van Vliet, Sandra J.
Rombouts, Yoann
Sciacca, Agnese
de Ru, Arnoud H.
Janssen, George M. C.
Tjokrodirijo, Rayman T. N.
Wuhrer, Manfred
van Veelen, Peter A.
Hensbergen, Paul J.
author_sort Pirro, Martina
collection PubMed
description Colorectal cancer (CRC) is the second-leading cause of cancer death worldwide due in part to a high proportion of patients diagnosed at advanced stages of the disease. For this reason, many efforts have been made towards new approaches for early detection and prognosis. Cancer-associated aberrant glycosylation, especially the Tn and STn antigens, can be detected using the macrophage galactose-type C-type lectin (MGL/CLEC10A/CD301), which has been shown to be a promising tool for CRC prognosis. We had recently identified the major MGL-binding glycoproteins in two high-MGL-binding CRC cells lines, HCT116 and HT29. However, we failed to detect the presence of O-linked Tn and STn glycans on most CRC glycoproteins recognized by MGL. We therefore investigated here the impact of N-linked and O-linked glycans carried by these proteins for the binding to MGL. In addition, we performed quantitative proteomics to study the major differences in proteins involved in glycosylation in these cells. Our results showed that N-glycans have a significant, previously underestimated, importance in MGL binding to CRC cell lines. Finally, we highlighted both common and cell-specific processes associated with a high-MGL-binding phenotype, such as differential levels of enzymes involved in protein glycosylation, and a transcriptional factor (CDX-2) involved in their regulation.
format Online
Article
Text
id pubmed-7432225
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-74322252020-08-24 N-Glycoproteins Have a Major Role in MGL Binding to Colorectal Cancer Cell Lines: Associations with Overall Proteome Diversity Pirro, Martina Mohammed, Yassene van Vliet, Sandra J. Rombouts, Yoann Sciacca, Agnese de Ru, Arnoud H. Janssen, George M. C. Tjokrodirijo, Rayman T. N. Wuhrer, Manfred van Veelen, Peter A. Hensbergen, Paul J. Int J Mol Sci Article Colorectal cancer (CRC) is the second-leading cause of cancer death worldwide due in part to a high proportion of patients diagnosed at advanced stages of the disease. For this reason, many efforts have been made towards new approaches for early detection and prognosis. Cancer-associated aberrant glycosylation, especially the Tn and STn antigens, can be detected using the macrophage galactose-type C-type lectin (MGL/CLEC10A/CD301), which has been shown to be a promising tool for CRC prognosis. We had recently identified the major MGL-binding glycoproteins in two high-MGL-binding CRC cells lines, HCT116 and HT29. However, we failed to detect the presence of O-linked Tn and STn glycans on most CRC glycoproteins recognized by MGL. We therefore investigated here the impact of N-linked and O-linked glycans carried by these proteins for the binding to MGL. In addition, we performed quantitative proteomics to study the major differences in proteins involved in glycosylation in these cells. Our results showed that N-glycans have a significant, previously underestimated, importance in MGL binding to CRC cell lines. Finally, we highlighted both common and cell-specific processes associated with a high-MGL-binding phenotype, such as differential levels of enzymes involved in protein glycosylation, and a transcriptional factor (CDX-2) involved in their regulation. MDPI 2020-08-01 /pmc/articles/PMC7432225/ /pubmed/32752259 http://dx.doi.org/10.3390/ijms21155522 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pirro, Martina
Mohammed, Yassene
van Vliet, Sandra J.
Rombouts, Yoann
Sciacca, Agnese
de Ru, Arnoud H.
Janssen, George M. C.
Tjokrodirijo, Rayman T. N.
Wuhrer, Manfred
van Veelen, Peter A.
Hensbergen, Paul J.
N-Glycoproteins Have a Major Role in MGL Binding to Colorectal Cancer Cell Lines: Associations with Overall Proteome Diversity
title N-Glycoproteins Have a Major Role in MGL Binding to Colorectal Cancer Cell Lines: Associations with Overall Proteome Diversity
title_full N-Glycoproteins Have a Major Role in MGL Binding to Colorectal Cancer Cell Lines: Associations with Overall Proteome Diversity
title_fullStr N-Glycoproteins Have a Major Role in MGL Binding to Colorectal Cancer Cell Lines: Associations with Overall Proteome Diversity
title_full_unstemmed N-Glycoproteins Have a Major Role in MGL Binding to Colorectal Cancer Cell Lines: Associations with Overall Proteome Diversity
title_short N-Glycoproteins Have a Major Role in MGL Binding to Colorectal Cancer Cell Lines: Associations with Overall Proteome Diversity
title_sort n-glycoproteins have a major role in mgl binding to colorectal cancer cell lines: associations with overall proteome diversity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432225/
https://www.ncbi.nlm.nih.gov/pubmed/32752259
http://dx.doi.org/10.3390/ijms21155522
work_keys_str_mv AT pirromartina nglycoproteinshaveamajorroleinmglbindingtocolorectalcancercelllinesassociationswithoverallproteomediversity
AT mohammedyassene nglycoproteinshaveamajorroleinmglbindingtocolorectalcancercelllinesassociationswithoverallproteomediversity
AT vanvlietsandraj nglycoproteinshaveamajorroleinmglbindingtocolorectalcancercelllinesassociationswithoverallproteomediversity
AT romboutsyoann nglycoproteinshaveamajorroleinmglbindingtocolorectalcancercelllinesassociationswithoverallproteomediversity
AT sciaccaagnese nglycoproteinshaveamajorroleinmglbindingtocolorectalcancercelllinesassociationswithoverallproteomediversity
AT deruarnoudh nglycoproteinshaveamajorroleinmglbindingtocolorectalcancercelllinesassociationswithoverallproteomediversity
AT janssengeorgemc nglycoproteinshaveamajorroleinmglbindingtocolorectalcancercelllinesassociationswithoverallproteomediversity
AT tjokrodirijoraymantn nglycoproteinshaveamajorroleinmglbindingtocolorectalcancercelllinesassociationswithoverallproteomediversity
AT wuhrermanfred nglycoproteinshaveamajorroleinmglbindingtocolorectalcancercelllinesassociationswithoverallproteomediversity
AT vanveelenpetera nglycoproteinshaveamajorroleinmglbindingtocolorectalcancercelllinesassociationswithoverallproteomediversity
AT hensbergenpaulj nglycoproteinshaveamajorroleinmglbindingtocolorectalcancercelllinesassociationswithoverallproteomediversity