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 & 14 others 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

Research output: Contribution to journalArticleResearchpeer-review

Abstract

While aberrant protein glycosylation is a recognised characteristic of human cancers, advances in glycoanalytics continue to discover new associations between glycoproteins and tumourigenesis. This glycomics‐centric study investigates a possible link between protein paucimannosylation, an under‐studied class of human N‐glycosylation [Man1‐3GlcNAc2Fuc0‐1], and human cancers. The paucimannosidic glycans (PMGs) of 34 cancer cell lines and 133 tissue samples spanning 11 cancer types and matching non‐cancerous specimens were profiled from 467 published and unpublished PGC‐LC‐MS/MS N‐glycome datasets collected over a decade within our laboratories. PMGs, particularly Man2‐3GlcNAc2Fuc1, were prominent features of 29 cancer cell lines, but the PMG level varied dramatically across and within the investigated cancer types (1.0%‐50.2%). Analyses of paired (tumour/non‐tumour) and stage‐stratified tissues demonstrated that PMGs are significantly enriched in tumour 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 was demonstrated on human glioblastoma cells using immunofluorescence while biosynthetic involvement of N‐acetyl‐β‐hexosaminidase was 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 tumourigenesis and metastasis.
LanguageEnglish
JournalProteomics
DOIs
Publication statusAccepted/In press - 16 Aug 2019

Fingerprint

Glycosylation
Polysaccharides
Tumors
Tissue
Neoplasms
Proteins
Cells
beta-N-Acetylhexosaminidases
Biosynthesis
Liver
Epitopes
Liver Neoplasms
Glycoproteins
Carrier Proteins
Association reactions
Glycomics
Cell Line
B-Cell Chronic Lymphocytic Leukemia
Glioblastoma
Proteomics

Keywords

  • Cancer
  • glycan
  • glycomics
  • paucimannosidic glycan
  • protein paucimannosylation

Cite this

Chatterjee, Sayantani ; Lee, Ling Y. ; Kawahara, Rebeca ; Abrahams, Jodie L. ; Adamczyk, Barbara ; Anugraham, Merrina ; Ashwood, Christopher ; Sumer-Bayraktar, Zeynep ; Briggs, Matthew T. ; Chik, Jenny H. L. ; Everest-Dass, Arun ; Förster, Sarah ; Hinneburg, Hannes ; Leite, Katia R. M. ; Loke, Ian ; Möginger, Uwe ; Moh, Edward S. X. ; Nakano, Miyako ; Recuero, Saulo ; Sethi, Manveen K. ; Srougi, Miguel ; Stavenhagen, Kathrin ; Venkatakrishnan, Vignesh ; Wongtrakul-Kish, Katherine ; Diestel, Simone ; Hoffmann, Peter ; Karlsson, Niclas G. ; Kolarich, Daniel ; Molloy, Mark P. ; Muders, Michael H. ; Oehler, Martin K. ; Packer, Nicolle H. ; Palmisano, Giuseppe ; Thaysen-Andersen, Morten. / Protein paucimannosylation is an enriched N-glycosylation signature of human cancers. In: Proteomics. 2019.
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title = "Protein paucimannosylation is an enriched N-glycosylation signature of human cancers",
abstract = "While aberrant protein glycosylation is a recognised characteristic of human cancers, advances in glycoanalytics continue to discover new associations between glycoproteins and tumourigenesis. This glycomics‐centric study investigates a possible link between protein paucimannosylation, an under‐studied class of human N‐glycosylation [Man1‐3GlcNAc2Fuc0‐1], and human cancers. The paucimannosidic glycans (PMGs) of 34 cancer cell lines and 133 tissue samples spanning 11 cancer types and matching non‐cancerous specimens were profiled from 467 published and unpublished PGC‐LC‐MS/MS N‐glycome datasets collected over a decade within our laboratories. PMGs, particularly Man2‐3GlcNAc2Fuc1, were prominent features of 29 cancer cell lines, but the PMG level varied dramatically across and within the investigated cancer types (1.0{\%}‐50.2{\%}). Analyses of paired (tumour/non‐tumour) and stage‐stratified tissues demonstrated that PMGs are significantly enriched in tumour 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 was demonstrated on human glioblastoma cells using immunofluorescence while biosynthetic involvement of N‐acetyl‐β‐hexosaminidase was 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 tumourigenesis and metastasis.",
keywords = "Cancer, glycan, glycomics, paucimannosidic glycan, protein paucimannosylation",
author = "Sayantani Chatterjee and Lee, {Ling Y.} and Rebeca Kawahara and Abrahams, {Jodie L.} and Barbara Adamczyk and Merrina Anugraham and Christopher Ashwood and Zeynep Sumer-Bayraktar and Briggs, {Matthew T.} and Chik, {Jenny H. L.} and Arun Everest-Dass and Sarah F{\"o}rster and Hannes Hinneburg and Leite, {Katia R. M.} and Ian Loke and Uwe M{\"o}ginger and Moh, {Edward S. X.} and Miyako Nakano and Saulo Recuero and Sethi, {Manveen K.} and Miguel Srougi and Kathrin Stavenhagen and Vignesh Venkatakrishnan and Katherine Wongtrakul-Kish and Simone Diestel and Peter Hoffmann and Karlsson, {Niclas G.} and Daniel Kolarich and Molloy, {Mark P.} and Muders, {Michael H.} and Oehler, {Martin K.} and Packer, {Nicolle H.} and Giuseppe Palmisano and Morten Thaysen-Andersen",
year = "2019",
month = "8",
day = "16",
doi = "10.1002/pmic.201900010",
language = "English",
journal = "Proteomics",
issn = "1615-9853",
publisher = "Wiley-Liss, Wiley",

}

Chatterjee, S, Lee, LY, Kawahara, R, Abrahams, JL, Adamczyk, B, Anugraham, M, Ashwood, C, Sumer-Bayraktar, Z, Briggs, MT, Chik, JHL, Everest-Dass, A, Förster, S, Hinneburg, H, Leite, KRM, Loke, I, Möginger, U, Moh, ESX, Nakano, M, Recuero, S, Sethi, MK, Srougi, M, Stavenhagen, K, Venkatakrishnan, V, Wongtrakul-Kish, K, Diestel, S, Hoffmann, P, Karlsson, NG, Kolarich, D, Molloy, MP, Muders, MH, Oehler, MK, Packer, NH, Palmisano, G & Thaysen-Andersen, M 2019, 'Protein paucimannosylation is an enriched N-glycosylation signature of human cancers' Proteomics. https://doi.org/10.1002/pmic.201900010

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

In: Proteomics, 16.08.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Protein paucimannosylation is an enriched N-glycosylation signature of human cancers

AU - Chatterjee,Sayantani

AU - Lee,Ling Y.

AU - Kawahara,Rebeca

AU - Abrahams,Jodie L.

AU - Adamczyk,Barbara

AU - Anugraham,Merrina

AU - Ashwood,Christopher

AU - Sumer-Bayraktar,Zeynep

AU - Briggs,Matthew T.

AU - Chik,Jenny H. L.

AU - Everest-Dass,Arun

AU - Förster,Sarah

AU - Hinneburg,Hannes

AU - Leite,Katia R. M.

AU - Loke,Ian

AU - Möginger,Uwe

AU - Moh,Edward S. X.

AU - Nakano,Miyako

AU - Recuero,Saulo

AU - Sethi,Manveen K.

AU - Srougi,Miguel

AU - Stavenhagen,Kathrin

AU - Venkatakrishnan,Vignesh

AU - Wongtrakul-Kish,Katherine

AU - Diestel,Simone

AU - Hoffmann,Peter

AU - Karlsson,Niclas G.

AU - Kolarich,Daniel

AU - Molloy,Mark P.

AU - Muders,Michael H.

AU - Oehler,Martin K.

AU - Packer,Nicolle H.

AU - Palmisano,Giuseppe

AU - Thaysen-Andersen,Morten

PY - 2019/8/16

Y1 - 2019/8/16

N2 - While aberrant protein glycosylation is a recognised characteristic of human cancers, advances in glycoanalytics continue to discover new associations between glycoproteins and tumourigenesis. This glycomics‐centric study investigates a possible link between protein paucimannosylation, an under‐studied class of human N‐glycosylation [Man1‐3GlcNAc2Fuc0‐1], and human cancers. The paucimannosidic glycans (PMGs) of 34 cancer cell lines and 133 tissue samples spanning 11 cancer types and matching non‐cancerous specimens were profiled from 467 published and unpublished PGC‐LC‐MS/MS N‐glycome datasets collected over a decade within our laboratories. PMGs, particularly Man2‐3GlcNAc2Fuc1, were prominent features of 29 cancer cell lines, but the PMG level varied dramatically across and within the investigated cancer types (1.0%‐50.2%). Analyses of paired (tumour/non‐tumour) and stage‐stratified tissues demonstrated that PMGs are significantly enriched in tumour 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 was demonstrated on human glioblastoma cells using immunofluorescence while biosynthetic involvement of N‐acetyl‐β‐hexosaminidase was 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 tumourigenesis and metastasis.

AB - While aberrant protein glycosylation is a recognised characteristic of human cancers, advances in glycoanalytics continue to discover new associations between glycoproteins and tumourigenesis. This glycomics‐centric study investigates a possible link between protein paucimannosylation, an under‐studied class of human N‐glycosylation [Man1‐3GlcNAc2Fuc0‐1], and human cancers. The paucimannosidic glycans (PMGs) of 34 cancer cell lines and 133 tissue samples spanning 11 cancer types and matching non‐cancerous specimens were profiled from 467 published and unpublished PGC‐LC‐MS/MS N‐glycome datasets collected over a decade within our laboratories. PMGs, particularly Man2‐3GlcNAc2Fuc1, were prominent features of 29 cancer cell lines, but the PMG level varied dramatically across and within the investigated cancer types (1.0%‐50.2%). Analyses of paired (tumour/non‐tumour) and stage‐stratified tissues demonstrated that PMGs are significantly enriched in tumour 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 was demonstrated on human glioblastoma cells using immunofluorescence while biosynthetic involvement of N‐acetyl‐β‐hexosaminidase was 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 tumourigenesis and metastasis.

KW - Cancer

KW - glycan

KW - glycomics

KW - paucimannosidic glycan

KW - protein paucimannosylation

U2 - 10.1002/pmic.201900010

DO - 10.1002/pmic.201900010

M3 - Article

JO - Proteomics

T2 - Proteomics

JF - Proteomics

SN - 1615-9853

ER -