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

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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 ; Foerster, Sarah ; Hinneburg, Hannes ; Leite, Katia R. M. ; Loke, Ian ; Moginger, 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

• Tipo de documento: Artigo Científico
• Fonte: PROTEOMICS; v. 19, n. 21-22, p. 13-pg., 2019-10-16.

Resumo

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133 tissue samples spanning 11 cancer types and matching non-cancerous specimens are profiled from 467 published and unpublished PGC-LC-MS/MS N-glycome datasets collected over a decade.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)

• Processo FAPESP: 18/15549-1 - Modificações pós-traducionais nos processos biológicos e no diagnóstico da Doença de Chagas: novas abordagens metodológicas e implicações biológicas
• Beneficiário: Giuseppe Palmisano
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2
• Processo FAPESP: 17/03010-8 - Caracterização sítio-específica de proteínas glicosiladas N e O-ligadas em tecidos de câncer de próstata como marcadores moleculares de progressão da doença
• Beneficiário: Rebeca Kawahara Sakuma
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 14/06863-3 - Modificações pós-traducionais para o diagnóstico de câncer e doenças parasitárias: abordagens metodológicas e implicações biológicas
• Beneficiário: Giuseppe Palmisano
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 15/02866-0 - Descoberta e verificação de glicopeptídeos intactos como candidatos à biomarcadores em câncer de próstata utilizando abordagens de proteômica-baseada em espectrometria de massas
• Beneficiário: Rebeca Kawahara Sakuma
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado