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

Artikel i vetenskaplig tidskrift
Författare S. Chatterjee
L. Y. Lee
R. Kawahara
J. L. Abrahams
Barbara Adamczyk
M. Anugraham
C. Ashwood
Z. Sumer-Bayraktar
M. T. Briggs
J. H. L. Chik
A. Everest-Dass
S. Forster
H. Hinneburg
K. R. M. Leite
I. Loke
U. Moginger
E. S. X. Moh
M. Nakano
S. Recuero
M. K. Sethi
M. Srougi
K. Stavenhagen
Vignes Venkatakrishnan
K. Wongtrakul-Kish
S. Diestel
P. Hoffmann
Niclas G. Karlsson
D. Kolarich
M. P. Molloy
M. H. Muders
M. K. Oehler
N. H. Packer
G. Palmisano
M. Thaysen-Andersen
Publicerad i Proteomics
ISSN 1615-9853
Publiceringsår 2019
Publicerad vid Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning
Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi
Språk en
Länkar dx.doi.org/10.1002/pmic.201900010
Ämnesord cancer, glycan, glycomics, paucimannosidic glycan, protein, paucimannosylation, paired colorectal-cancer, cell-lines, mucin glycosylation, structural-analysis, glycan, glycome, differentiation, inflammation, fucosylation, progression, Biochemistry & Molecular Biology
Ämneskategorier Biokemi och molekylärbiologi

Sammanfattning

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 [Man1‐3GlcNAc2Fuc0‐1], 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133 tissue samples spanning 11 cancer types and matching non‐cancerous specimens are profiled from 467 published and unpublished PGC‐LC‐MS/MS N‐glycome datasets collected over a decade.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 Man2‐3GlcNAc2Fuc1, 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.

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