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

Author(s):Show less -

Chatterjee, Sayantani ^{[1, 2]} ; Lee, Ling Y. ^{[1, 2, 3]} ; Kawahara, Rebeca ^{[1, 2, 4]} ; Abrahams, Jodie L. ^{[1, 2, 5]} ; Adamczyk, Barbara ^[6] ; Anugraham, Merrina ^{[1, 2, 7]} ; Ashwood, Christopher ^{[1, 2, 8]} ; Sumer-Bayraktar, Zeynep ^{[1, 2, 9]} ; Briggs, Matthew T. ^[10] ; Chik, Jenny H. L. ^{[11, 1, 2, 12]} ; Everest-Dass, Arun ^{[1, 2, 5]} ; Foerster, Sarah ^[13] ; Hinneburg, Hannes ^{[1, 2]} ; Leite, Katia R. M. ^[14] ; Loke, Ian ^{[1, 2, 15]} ; Moginger, Uwe ^[16] ; Moh, Edward S. X. ^{[1, 2, 17]} ; Nakano, Miyako ^{[1, 2, 18]} ; Recuero, Saulo ^[14] ; Sethi, Manveen K. ^{[1, 2, 19]} ; Srougi, Miguel ^[14] ; Stavenhagen, Kathrin ^{[20, 1, 2, 21]} ; Venkatakrishnan, Vignesh ^[22] ; Wongtrakul-Kish, Katherine ^{[1, 2, 23]} ; Diestel, Simone ^[24] ; Hoffmann, Peter ^[10] ; Karlsson, Niclas G. ^[6] ; Kolarich, Daniel ^[5] ; Molloy, Mark P. ^{[1, 2, 25]} ; Muders, Michael H. ^[13] ; Oehler, Martin K. ^[26] ; Packer, Nicolle H. ^{[1, 2, 5, 17]} ; Palmisano, Giuseppe ^[4] ; Thaysen-Andersen, Morten ^{[1, 2]}

Affiliation:Show less -

^[1] Macquarie Univ, Dept Mol Sci, Sydney, NSW 2109 - Australia

^[2] Macquarie Univ, BDDRC, Sydney, NSW 2109 - Australia

^[3] Univ Barcelona, Hosp Clin, Barcelona Ctr Int Hlth Res CRESIB, ISGlobal, Barcelona 08193 - Spain

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, BR-01000 Sao Paulo - Brazil

^[5] Griffith Univ, Inst Glyc, Gold Coast 4222 - Australia

^[6] Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Med Biochem & Cell Biol, SE-40530 Gothenburg - Sweden

^[7] Acad Sinica, Inst Biol Chem, Taipei 11529 - Taiwan

^[8] Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 - USA

^[9] Univ Sydney, CPC, Sch Life & Environm Sci, Sydney, NSW 2006 - Australia

^[10] Univ South Australia, Future Ind Inst, Mawson Lakes Campus, Adelaide, SA 5005 - Australia

^[11] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 1Z4 - Canada

^[12] Univ British Columbia, Int Collaborat Repair Discoveries Vancouver Coast, Vancouver, BC V6T 1Z4 - Canada

^[13] Univ Hosp Bonn, Inst Pathol, Rudolf Becker Lab, D-53127 Bonn - Germany

^[14] Univ Sao Paulo, Fac Med FMUSP, Lab Invest Med Disciplina Urol LIM55, BR-01000 Sao Paulo - Brazil

^[15] Natl Univ Singapore, Dept Biol Sci, Singapore 119077 - Singapore

^[16] Univ Southern Denmark, Dept Biochem & Mol Biol, DK-5230 Odense - Denmark

^[17] Macquarie Univ, ARC Ctr Nanoscale Biophoton, Sydney, NSW 2109 - Australia

^[18] Hiroshima Univ, Grad Sch Adv Sci Matter, Hiroshima 7398527 - Japan

^[19] Boston Univ, Sch Med, Dept Biochem, Ctr Biomed Mass Spectrometry, Boston, MA 02215 - USA

^[20] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 - USA

^[21] Harvard Med Sch, Ctr Glycosci, Boston, MA 02215 - USA

^[22] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, SE-40530 Gothenburg - Sweden

^[23] ASTAR, Bioproc Technol Inst, Singapore 13862 - Singapore

^[24] Univ Bonn, Inst Nutr & Food Sci, D-53127 Bonn - Germany

^[25] Royal North Shore Hosp, Sydney Sch Med, Fac Med & Hlth, Sydney, NSW 2065 - Australia

^[26] Royal Adelaide Hosp, Dept Gynaecol Oncol, Adelaide, SA 5000 - Australia

• Document type: Journal article
• Source: PROTEOMICS; v. 19, n. 21-22, SI NOV 2019.
• Web of Science Citations: 2

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)GlcNAc(2)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)GlcNAc(2)Fuc(1), 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-beta-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. (AU)

• FAPESP's process: 17/03010-8 - Site-specific characterization of N- and O-linked glycosylation in prostate cancer tissues as molecular signature for disease progression
• Grantee: Rebeca Kawahara Sakuma
• Support type: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 15/02866-0 - DISCOVERY AND VERIFICATION OF INTACT GLYCOPEPTIDES AS CANDIDATE PROSTATE CANCER BIOMARKERS USING MASS SPECTROMETRY-BASED PROTEOMICS APPROACHES
• Grantee: Rebeca Kawahara Sakuma
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 18/15549-1 - Post-translational modifications in Chagas Disease biological processes and diagnostics: novel methodological approaches and biological applications
• Grantee: Giuseppe Palmisano
• Support type: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 14/06863-3 - Post-translational modifications in cancer and parasite infection diagnosis: methodological approaches and biological implications
• Grantee: Giuseppe Palmisano
• Support type: Research Grants - Young Investigators Grants