Till sidans topp

Sidansvarig: Webbredaktion
Sidan uppdaterades: 2012-09-11 15:12

Tipsa en vän
Utskriftsversion

Glycomic analysis of gast… - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

Glycomic analysis of gastric carcinoma cells discloses glycans as modulators of RON receptor tyrosine kinase activation in cancer

Artikel i vetenskaplig tidskrift
Författare S. Mereiter
A. Magalhaes
Barbara Adamczyk
Chunsheng Jin
A. Almeida
L. Drici
M. Ibanez-Vea
C. Gomes
J. A. Ferreira
L. P. Afonso
L. L. Santos
M. R. Larsen
D. Kolarich
Niclas G. Karlsson
C. A. Reis
Publicerad i Biochimica Et Biophysica Acta-General Subjects
Volym 1860
Nummer/häfte 8
Sidor 1795-1808
ISSN 0304-4165
Publiceringsår 2016
Publicerad vid Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi
Sidor 1795-1808
Språk en
Länkar dx.doi.org/10.1016/j.bbagen.2015.12...
Ämnesord ST3GAL4, Sialyl Lewis X (SLeX), RON, Gastric cancer, Glycome, Sialome, n-acetylglucosaminyltransferase-iii, c-met, breast-cancer, linked, oligosaccharides, personalized medicine, structural-analysis, colorectal-cancer, invasive growth, next-generation, in-vivo, Biochemistry & Molecular Biology, Biophysics
Ämneskategorier Biofysik, Biokemi och molekylärbiologi

Sammanfattning

Background: Terminal alpha 2-3 and alpha 2-6 sialylation of glycans precludes further chain elongation, leading to the biosynthesis of cancer relevant epitopes such as sialyl-Lewis X (SLe(X)). SLe(X) overexpression is associated with tumor aggressive phenotype and patients' poor prognosis. Methods: MKN45 gastric carcinoma cells transfected with the sialyltransferase ST3GAL4 were established as a model overexpressing sialylated terminal glycans. We have evaluated at the structural level the glycome and the sialoproteome of this gastric cancer cell line applying liquid chromatography and mass spectrometry. We further validated an identified target expression by proximity ligation assay in gastric tumors. Results: Our results showed that ST3GAL4 overexpression leads to several glycosylation alterations, including reduced O-glycan extension and decreased bisected and increased branched N-glycans. A shift from alpha 2-6 towards alpha 2-3 linked sialylated N-glycans was also observed. Sialoproteomic analysis further identified 47 proteins with significantly increased sialylated N-glycans. These included integrins, insulin receptor, carcinoembryonic antigens and RON receptor tyrosine kinase, which are proteins known to be key players in malignancy. Further analysis of RON confirmed its modification with SLe(X) and the concomitant activation. SLe(X) and RON co-expression was validated in gastric tumors. Conclusion: The overexpression of ST3GAL4 interferes with the overall glycophenotype of cancer cells affecting a multitude of key proteins involved in malignancy. Aberrant glycosylation of the RON receptor was shown as an alternative mechanism of oncogenic activation. General significance: This study provides novel targets and points to an integrative tumor glycomic/proteomic-profiling for gastric cancer patients' stratification. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?