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Bladder Tumours O-Glycoproteomics

ABSTRACT: Bladder carcinogenesis and tumour progression is accompanied by profound alterations in protein glycosylation. These include the presence of short chain O-glycans such as Tn and T antigens and their sialylated counterparts sialyl-Tn(STn) and sialyl-T(ST). The presence of such structures is commonly associated with poor prognosis. In search for prognosis biomarkers and novel therapeutic targets we have screened, using immunohistochemistry, a series of bladder tumours with differing clinicopathology for these short-chain O-glycans. Aiming at identifying protein targets, we have studied the O-glycoproteome of a pool of STn positive tumours from muscle invasive bladder cancer (MIBC) patients.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Bladder

DISEASE(S): Urinary Bladder Cancer

SUBMITTER: André Silva

LAB HEAD: José Alexandre Ferreira

PROVIDER: PXD006813 | Pride | 2017-08-17

REPOSITORIES: Pride

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			Action	DRS
	Stn_Exp1.raw	Raw
	Stn_Exp2.raw	Raw
	Stn_Exp3.raw	Raw
	Stn_Exp4.raw	Raw
	Stn_TnT.msf	Msf

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Publications

In silico approaches for unveiling novel glycobiomarkers in cancer.

Azevedo Rita R Silva André M N AMN Reis Celso A CA Santos Lúcio Lara LL Ferreira José Alexandre JA

Journal of proteomics 20170804

Glycosylation is one of the most common and dynamic post-translational modification of cell surface and secreted proteins. Cancer cells display unique glycosylation patterns that decisively contribute to drive oncogenic behavior, including disease progression and dissemination. Moreover, alterations in glycosylation are often responsible for the creation of protein signatures holding significant biomarker value and potential for targeted therapeutics. Accordingly, many analytical protocols have ...[more]

PMID: 28782717

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O-linked glicoproteomics of gastric cancer cell lines OCUM-1, N87 and KATO-III

Project description:Gastric cancer (GC) is the third leading cause of cancer-related death worldwide, continuously requiring innovative target therapies. The sialyl-lewis A (SLeA) antigen offers tremendous potential for precise cancer targeting. This glycan is rarely expressed by healthy tissues and blood cells but is often present in cancer cells of high metastatic potential as well as in the metastasis. To improve further on the gastric cancer nature of this glycan we have zoomed in on the SLeA-glycoproteome envisaging the identification of possible targetable biomarkers. SLeA-glycoproteins were isolated by immunoprecipitation from well-known cell models of gastric cancer reflecting different histological subtypes of the disease (KATO-III, OCUM-1 and N87 cells). Glycoproteins with affinity for E-selectin were also isolated and analyzed. Proteomics study employed a typical nanoLC-ESI-Orbitrap-MS/MS platform. The well-known molecular heterogeneity of these cell lines was reflected in the markedly different glycoproteomics signatures observed. Nevertheless, a restricted panel of SLeA-expressing glycoproteins with affinity for E-selectin remained conserved between the cell lines, consisting of a promising list of potentially targetable biomarkers for bladder cancer.

2020-05-11 | PXD016968 | Pride

EXoO-Tn: Tag-n-Map the Tn Antigen in the Human Proteome

Project description:Tn antigen (Tn), a single N-acetylgalactosamine (GalNAc) monosaccharide attached to protein Ser and Thr residues, is found on most solid tumors yet rarely detected in adult tissues: featuring it one of the most distinctive signatures of cancers. Although it is prevalent in cancers, Tn-glycosylation sites are not entirely clear owing to the lack of suitable technology. Knowing the Tn-glycosylation sites will spur the development of the new vaccines, diagnostics, and therapeutics of cancers. Here, we report a novel technology named EXoO-Tn for large-scale mapping of Tn-glycosylation sites. EXoO-Tn utilizes glycosyltransferase C1GalT1 and isotopically-labeled UDP-Gal(13C6) to tag and convert Tn to Gal(13C6)-Tn. This exquisite Gal(13C6)-Tn structure is recognized by a human-gut-bacterial enzyme, called OpeRATOR, that specifically cleaves N-termini of the Gal(13C6)-Tn-occupied Ser and Thr residues to yield site-containing glycopeptides. The enzymes C1GalT1 and OpeRATOR could be used concurrently in one-pot. The effectiveness of EXoO-Tn was evaluated by analyzing Jurkat cells, where 947 Tn-glycosylation sites from 480 glycoproteins were mapped. Bioinformatic analysis of the identified site-specific Tn-glycoproteins revealed conserved motif, cellular localization, relative position in proteins, and mapped site-specific Tn-glycoproteome in different studies. Given the significance of Tn in cancers, EXoO-Tn is anticipated to have broad utilities in clinical study of cancers.

2022-02-15 | PXD014390 | Pride

Structural insights into Siglec-15 reveal glycosylation dependency for its interaction with T cells through integrin CD11b

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2023-07-20 | PXD042009 | Pride

Expression profiling in primary embryonic fibroblasts deficient for the N-terminal truncation of Lats1

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2012-12-17 | E-GEOD-37871 | biostudies-arrayexpress

Human holo-transferrin glycation

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