Glucose Metabolism Reprogramming in Bladder Cancer: Hexokinase 2 (HK2) as Prognostic Biomarker and Target for Bladder Cancer Therapy

Registro completo de metadados
MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversity of Minho-
Autor(es): dc.contributorICVS/3B’s—PT Government Associate Laboratory-
Autor(es): dc.contributorLABBELS—Associate Laboratory-
Autor(es): dc.contributorResearch Center of the Portuguese Institute of Oncology (CI-IPOP)-
Autor(es): dc.contributorPorto Comprehensive Cancer Center (P.CCC)-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorBarretos Cancer Hospital-
Autor(es): dc.creatorAfonso, Julieta-
Autor(es): dc.creatorGonçalves, Céline-
Autor(es): dc.creatorCosta, Marta-
Autor(es): dc.creatorFerreira, Débora-
Autor(es): dc.creatorSantos, Lúcio-
Autor(es): dc.creatorLongatto-Filho, Adhemar-
Autor(es): dc.creatorBaltazar, Fátima-
Data de aceite: dc.date.accessioned2025-08-21T19:00:26Z-
Data de disponibilização: dc.date.available2025-08-21T19:00:26Z-
Data de envio: dc.date.issued2023-07-29-
Data de envio: dc.date.issued2023-07-29-
Data de envio: dc.date.issued2023-01-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/cancers15030982-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/246807-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/246807-
Descrição: dc.descriptionProliferating cancer cells are able to reprogram their energy metabolism, favouring glycolysis even in the presence of oxygen and fully functioning mitochondria. Research is needed to validate the glycolysis-related proteins as prognostic/predictive biomarkers in urothelial bladder carcinoma (UBC), a malignancy tagged by high recurrence rates and poor response to chemotherapy. Here, we assessed GLUT1, HK2, PFKL, PKM2, phospho-PDH, and LDHA immunoexpression in 76 UBC samples, differentiating among urothelial, fibroblast, and endothelial cells and among normoxic versus hypoxic areas. We additionally studied the functional effects of the HK2 inhibitor 2-deoxy-D-glucose (2DG) in “in vitro” and “in vivo” preclinical UBC models. We showed that the expression of the glycolysis-related proteins is associated with UBC aggressiveness and poor prognosis. HK2 remained as an independent prognostic factor for disease-free and overall survival. 2DG decreased the UBC cell’s viability, proliferation, migration, and invasion; the inhibition of cell cycle progression and apoptosis occurrence was also verified. A significant reduction in tumour growth and blood vessel formation upon 2DG treatment was observed in the chick chorioallantoic membrane assay. 2DG potentiated the cisplatin-induced inhibition of cell viability in a cisplatin-resistant subline. This study highlights HK2 as a prognostic biomarker for UBC patients and demonstrates the potential benefits of using 2DG as a glycolysis inhibitor. Future studies should focus on integrating 2DG into chemotherapy design, as an attempt to overcome cisplatin resistance.-
Descrição: dc.descriptionFuel Cell Technologies Program-
Descrição: dc.descriptionFundació Catalana de Trasplantament-
Descrição: dc.descriptionFundação para a Ciência e a Tecnologia-
Descrição: dc.descriptionNuclear Fuel Cycle and Supply Chain-
Descrição: dc.descriptionFaculdade de Ciências e Tecnologia, Universidade Nova de Lisboa-
Descrição: dc.descriptionProgramme of Competitive Forestry Research for Development-
Descrição: dc.descriptionLife and Health Sciences Research Institute (ICVS) University of Minho, Campus of Gualtar-
Descrição: dc.descriptionICVS/3B’s—PT Government Associate Laboratory-
Descrição: dc.descriptionCentre of Biological Engineering (CEB) University of Minho, Campus of Gualtar-
Descrição: dc.descriptionLABBELS—Associate Laboratory-
Descrição: dc.descriptionExperimental Pathology and Therapeutics Group Research Center of the Portuguese Institute of Oncology (CI-IPOP)-
Descrição: dc.descriptionPorto Comprehensive Cancer Center (P.CCC)-
Descrição: dc.descriptionLaboratory of Medical Investigation (LIM14) Faculty of Medicine São Paulo State University-
Descrição: dc.descriptionMolecular Oncology Research Center Barretos Cancer Hospital-
Descrição: dc.descriptionLaboratory of Medical Investigation (LIM14) Faculty of Medicine São Paulo State University-
Descrição: dc.descriptionFuel Cell Technologies Program: 2021.02600.CEECIND-
Descrição: dc.descriptionFundació Catalana de Trasplantament: 2021.02600.CEECIND-
Descrição: dc.descriptionFundação para a Ciência e a Tecnologia: 2021.02600.CEECIND-
Descrição: dc.descriptionNuclear Fuel Cycle and Supply Chain: 2021.02600.CEECIND-
Descrição: dc.descriptionFaculdade de Ciências e Tecnologia, Universidade Nova de Lisboa: 2021.02600.CEECIND-
Descrição: dc.descriptionProgramme of Competitive Forestry Research for Development: CTTI-117/21-ICVS(1)-
Descrição: dc.descriptionFuel Cell Technologies Program: SFRH/BPD/116784/2016-
Descrição: dc.descriptionFundació Catalana de Trasplantament: SFRH/BPD/116784/2016-
Descrição: dc.descriptionFundação para a Ciência e a Tecnologia: SFRH/BPD/116784/2016-
Descrição: dc.descriptionNuclear Fuel Cycle and Supply Chain: SFRH/BPD/116784/2016-
Descrição: dc.descriptionFaculdade de Ciências e Tecnologia, Universidade Nova de Lisboa: SFRH/BPD/116784/2016-
Idioma: dc.languageen-
Relação: dc.relationCancers-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subject2-deoxy-D-glucose-
Palavras-chave: dc.subjectcisplatin resistance-
Palavras-chave: dc.subjectglycolysis-
Palavras-chave: dc.subjecthexokinase 2-
Palavras-chave: dc.subjecturothelial bladder carcinoma-
Palavras-chave: dc.subjectWarburg effect-
Título: dc.titleGlucose Metabolism Reprogramming in Bladder Cancer: Hexokinase 2 (HK2) as Prognostic Biomarker and Target for Bladder Cancer Therapy-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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