Protein Paucimannosylation is an Enriched N-glycosylation Signature of Human Cancers.

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 [Man1-3 GlcNAc2 Fuc0-1 ], 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133 tissue samples spanning 11 cancer types and matching non-cancerous specimens were profiled from 467 published and unpublished PGC-LC-MS/MS N-glycome datasets collected over a decade within our laboratories.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 Man2-3 GlcNAc2 Fuc1 , 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. This article is protected by copyright. All rights reserved.