Aberrantly Glycosylated GLUT1 as a Poor Prognosis Marker in Aggressive Bladder Cancer.

Autor: Ferreira E; Experimental Pathology and Therapeutics Group, Research Center of IPO-Porto (CI-IPOP), 4200-072 Porto, Portugal.; RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal., Ferreira D; Experimental Pathology and Therapeutics Group, Research Center of IPO-Porto (CI-IPOP), 4200-072 Porto, Portugal.; RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal.; ICBAS-Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal.; i3S-Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal.; INEB-Institute for Biomedical Engineering, University of Porto, 4200-135 Porto, Portugal., Relvas-Santos M; Experimental Pathology and Therapeutics Group, Research Center of IPO-Porto (CI-IPOP), 4200-072 Porto, Portugal.; RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal.; ICBAS-Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal.; i3S-Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal.; INEB-Institute for Biomedical Engineering, University of Porto, 4200-135 Porto, Portugal.; REQUIMTE-LAQV, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal., Freitas R; Experimental Pathology and Therapeutics Group, Research Center of IPO-Porto (CI-IPOP), 4200-072 Porto, Portugal.; RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal.; ICBAS-Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal.; i3S-Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal.; INEB-Institute for Biomedical Engineering, University of Porto, 4200-135 Porto, Portugal., Soares J; Experimental Pathology and Therapeutics Group, Research Center of IPO-Porto (CI-IPOP), 4200-072 Porto, Portugal.; RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal.; ICBAS-Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal., Azevedo R; Institut Pasteur, Proteomics Core Facility, MSBio UtechS, 75015 Paris, France., Afonso LP; Experimental Pathology and Therapeutics Group, Research Center of IPO-Porto (CI-IPOP), 4200-072 Porto, Portugal.; RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal., Lima L; Experimental Pathology and Therapeutics Group, Research Center of IPO-Porto (CI-IPOP), 4200-072 Porto, Portugal.; RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal., Santos B; Experimental Pathology and Therapeutics Group, Research Center of IPO-Porto (CI-IPOP), 4200-072 Porto, Portugal.; RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal., Gonçalves M; Experimental Pathology and Therapeutics Group, Research Center of IPO-Porto (CI-IPOP), 4200-072 Porto, Portugal.; RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal., Silva AMN; ICBAS-Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal.; REQUIMTE-LAQV, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal.; GlycoMatters Biotech, 4500-162 Espinho, Portugal., Santos LL; Experimental Pathology and Therapeutics Group, Research Center of IPO-Porto (CI-IPOP), 4200-072 Porto, Portugal.; RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal.; GlycoMatters Biotech, 4500-162 Espinho, Portugal.; Department of Surgical Oncology, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal., Peixoto A; Experimental Pathology and Therapeutics Group, Research Center of IPO-Porto (CI-IPOP), 4200-072 Porto, Portugal.; RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal.; i3S-Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal.; INEB-Institute for Biomedical Engineering, University of Porto, 4200-135 Porto, Portugal., Ferreira JA; Experimental Pathology and Therapeutics Group, Research Center of IPO-Porto (CI-IPOP), 4200-072 Porto, Portugal.; RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC Raquel Seruca), 4200-072 Porto, Portugal.; ICBAS-Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal.; GlycoMatters Biotech, 4500-162 Espinho, Portugal.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Mar 19; Vol. 25 (6). Date of Electronic Publication: 2024 Mar 19.
DOI: 10.3390/ijms25063462
Abstrakt: Muscle-invasive bladder cancer (MIBC) remains a pressing health concern due to conventional treatment failure and significant molecular heterogeneity, hampering the development of novel targeted therapeutics. In our quest for novel targetable markers, recent glycoproteomics and bioinformatics data have pinpointed (glucose transporter 1) GLUT1 as a potential biomarker due to its increased expression in tumours compared to healthy tissues. This study explores this hypothesis in more detail, with emphasis on GLUT1 glycosylation patterns and cancer specificity. Immunohistochemistry analysis across a diverse set of human bladder tumours representing all disease stages revealed increasing GLUT1 expression with lesion severity, extending to metastasis, while remaining undetectable in healthy urothelium. In line with this, GLUT1 emerged as a marker of reduced overall survival. Revisiting nanoLC-EThcD-MS/MS data targeting immature O -glycosylation on muscle-invasive tumours identified GLUT1 as a carrier of short glycosylation associated with invasive disease. Precise glycosite mapping uncovered significant heterogeneity between patient samples, but also common glycopatterns that could provide the molecular basis for targeted solutions. Immature O -glycosylation conferred cancer specificity to GLUT1, laying the molecular groundwork for enhanced targeted therapeutics in bladder cancer. Future studies should focus on a comprehensive mapping of GLUT1 glycosites for highly specific cancer-targeted therapy development for bladder cancer.
Databáze: MEDLINE
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