Trends in oligomannosylation and α1,2-mannosidase expression in human cancers

Sayantani Chatterjee, Julian Ugonotti, Ling Y. Lee, Arun Everest-Dass, Rebeca Kawahara Sakuma*, Morten Thaysen-Andersen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Aberrant protein glycosylation is a prominent cancer feature. While many tumour-associated glycoepitopes have been reported, advances in glycoanalytics continue to uncover new associations between glycosylation and cancer. Guided by a comprehensive literature survey suggesting that oligomannosylation (Man5–9 GlcNAc2) is a widespread and often regulated glycosignature in human cancers, we here revisit a valuable compilation of nearly 500 porous graphitized carbon LC-MS/MS N-glycomics datasets acquired across 11 human cancer types to systematically test for oligomannose-cancer associations. Firstly, the quantitative glycomics data obtained across 34 cancerous cell lines demonstrated that oligomannosylation is a pan-cancer feature spanning in a wide abundance range. In keeping with literature, our quantitative glycomics data of tumour and matching control tissues and new MALDI-MS imaging data of tissue microarrays showed a strong cancer-associated elevation of oligomannosylation in both basal cell (p = 1.78 × 10–12) and squamous cell (p = 1.23 × 10–11) skin cancer and colorectal cancer (p = 8.0 × 10–4). The glycomics data also indicated that some cancer types including gastric and liver cancer exhibit unchanged or reduced oligomannose levels, observations also supported by literature and MALDI-MS imaging data. Finally, expression data from public cancer repositories indicated that several α1,2-mannosidases are regulated in tumour tissues suggesting that these glycan-processing enzymes may contribute to the cancer-associated modulation of oligomannosylation. This omics-centric study has compiled robust glycomics and enzyme expression data revealing interesting molecular trends that open avenues to better understand the role of oligomannosylation in human cancers.
Original languageEnglish
JournalOncotarget
DOIs
Publication statusE-pub ahead of print - 18 Aug 2021

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