Protein Paucimannosylation Is an Enriched N-Glycosylation Signature of Human Cancers

Sayantani Chatterjee; Ling Y Lee; Rebeca Kawahara; Jodie L Abrahams; Barbara Adamczyk; Merrina Anugraham; Christopher Ashwood; Zeynep Sumer-Bayraktar; Matthew T Briggs; Jenny H L Chik; Arun Everest-Dass; Sarah Förster; Hannes Hinneburg; Katia R M Leite; Ian Loke; Uwe Möginger; Edward S X Moh; Miyako Nakano; Saulo Recuero; Manveen K Sethi; Miguel Srougi; Kathrin Stavenhagen; Vignesh Venkatakrishnan; Katherine Wongtrakul-Kish; Simone Diestel; Peter Hoffmann; Niclas G Karlsson; Daniel Kolarich; Mark P Molloy; Michael H Muders; Martin K Oehler; Nicolle H Packer; Giuseppe Palmisano; Morten Thaysen-Andersen

doi:10.1002/pmic.201900010

Protein Paucimannosylation Is an Enriched N-Glycosylation Signature of Human Cancers

Proteomics. 2019 Nov;19(21-22):e1900010. doi: 10.1002/pmic.201900010. Epub 2019 Oct 16.

Authors

Sayantani Chatterjee¹, Ling Y Lee^{1

2}, Rebeca Kawahara^{1

3}, Jodie L Abrahams^{1

4}, Barbara Adamczyk⁵, Merrina Anugraham^{1

6}, Christopher Ashwood^{1

7}, Zeynep Sumer-Bayraktar^{1

8}, Matthew T Briggs⁹, Jenny H L Chik^{1

10}, Arun Everest-Dass^{1

4}, Sarah Förster¹¹, Hannes Hinneburg¹, Katia R M Leite¹², Ian Loke^{1

13}, Uwe Möginger¹⁴, Edward S X Moh^{1

15}, Miyako Nakano^{1

16}, Saulo Recuero¹², Manveen K Sethi^{1

17}, Miguel Srougi¹², Kathrin Stavenhagen^{1

18}, Vignesh Venkatakrishnan¹⁹, Katherine Wongtrakul-Kish^{1

20}, Simone Diestel²¹, Peter Hoffmann⁹, Niclas G Karlsson⁵, Daniel Kolarich⁴, Mark P Molloy^{1

22}, Michael H Muders¹¹, Martin K Oehler²³, Nicolle H Packer^{1

4

15}, Giuseppe Palmisano³, Morten Thaysen-Andersen¹

Affiliations

¹ Department of Molecular Sciences and Biomolecular Discovery and Design Research Centre (BDDRC), Macquarie University, Sydney, 2109, Australia.
² ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, 08193, Spain.
³ Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, 01000, Brazil.
⁴ Institute for Glycomics, Griffith University, Gold Coast, 4222, Australia.
⁵ Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SE 405 30, Sweden.
⁶ Institute of Biological Chemistry, Academia Sinica, Taipei, 11529, Taiwan.
⁷ Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
⁸ School of Life and Environmental Sciences, Charles Perkins Centre (CPC), The University of Sydney, Sydney, 2006, Australia.
⁹ Future Industries Institute, Mawson Lakes Campus, University of South Australia, Adelaide, 5005, Australia.
¹⁰ International Collaboration on Repair Discoveries, Vancouver Coastal Health Research Institute and Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
¹¹ Rudolf-Becker-Laboratory, Institute of Pathology, University Hospital Bonn, Bonn, 53127, Germany.
¹² Laboratório de Investigação Médica da Disciplina de Urologia (LIM55), Faculdade de Medicina da FMUSP, Universidade de Sao Paulo, São Paulo, 01000, Brazil.
¹³ Department of Biological Sciences, National University of Singapore, Singapore, 119077, Singapore.
¹⁴ Department for Biochemistry and Molecular Biology, University of Southern Denmark, Odense, 5230, Denmark.
¹⁵ ARC Centre for Nanoscale Biophotonics, Macquarie University, Sydney, 2109, Australia.
¹⁶ Graduate School of Advanced Sciences of Matter, Hiroshima University, Hiroshima, 739-8527, Japan.
¹⁷ Center for Biomedical Mass Spectrometry, Department of Biochemistry, Boston University School of Medicine, Boston University, Boston, MA, 02215, USA.
¹⁸ Beth Israel Deaconess Medical Center, Department of Surgery and Harvard Medical School Center for Glycoscience, Harvard Medical School, Boston, MA, 02215, USA.
¹⁹ Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SE 405 30, Sweden.
²⁰ Bioprocessing Technology Institute, A*STAR, Singapore, 13862, Singapore.
²¹ Institute of Nutrition and Food Sciences, University of Bonn, Bonn, 53127, Germany.
²² Faculty of Medicine and Health, Sydney School of Medicine, Royal North Shore Hospital, Sydney, 2065, Australia.
²³ Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, 5000, Australia.

PMID: 31419058
DOI: 10.1002/pmic.201900010

Abstract

While aberrant protein glycosylation is a recognized characteristic of human cancers, advances in glycoanalytics continue to discover new associations between glycoproteins and tumorigenesis. This glycomics-centric study investigates a possible link between protein paucimannosylation, an under-studied class of human N-glycosylation [Man_1-3 GlcNAc₂ Fuc_0-1 ], and cancer. The paucimannosidic glycans (PMGs) of 34 cancer cell lines and 133 tissue samples spanning 11 cancer types and matching non-cancerous specimens are profiled from 467 published and unpublished PGC-LC-MS/MS N-glycome datasets collected over a decade. PMGs, particularly Man_2-3 GlcNAc₂ Fuc₁ , are prominent features of 29 cancer cell lines, but the PMG level varies dramatically across and within the cancer types (1.0-50.2%). Analyses of paired (tumor/non-tumor) and stage-stratified tissues demonstrate that PMGs are significantly enriched in tumor tissues from several cancer types including liver cancer (p = 0.0033) and colorectal cancer (p = 0.0017) and is elevated as a result of prostate cancer and chronic lymphocytic leukaemia progression (p < 0.05). Surface expression of paucimannosidic epitopes is demonstrated on human glioblastoma cells using immunofluorescence while biosynthetic involvement of N-acetyl-β-hexosaminidase is indicated by quantitative proteomics. This intriguing association between protein paucimannosylation and human cancers warrants further exploration to detail the biosynthesis, cellular location(s), protein carriers, and functions of paucimannosylation in tumorigenesis and metastasis.

Keywords: cancer; glycan; glycomics; paucimannosidic glycan; protein paucimannosylation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Chromatography, Liquid
Disease Progression
Glycosylation
Humans
Mannose / metabolism*
Neoplasms / metabolism*
Tandem Mass Spectrometry

Substances

Mannose