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https://hdl.handle.net/1822/82536
Título: | Glucose metabolism reprogramming in bladder cancer: hexokinase 2 (HK2) as prognostic biomarker and target for bladder cancer therapy |
Autor(es): | Afonso, Julieta Gonçalves, Céline Costa, Marta Ferreira, Débora Carina Gonçalves Abreu Santos, Lúcio Longatto-Filho, Adhemar Baltazar, Fátima |
Palavras-chave: | Warburg effect Glycolysis Hexokinase 2 2-deoxy-D-glucose Urothelial bladder carcinoma Cisplatin resistance |
Data: | Jan-2023 |
Editora: | Multidisciplinary Digital Publishing Institute (MDPI) |
Revista: | Cancers |
Citação: | Afonso, Julieta; Gonçalves, Céline; Costa, Marta; Ferreira, Débora; Santos, Lúcio; Longatto-Filho, Adhemar; Baltazar, Fátima, Glucose metabolism reprogramming in bladder cancer: hexokinase 2 (HK2) as prognostic biomarker and target for bladder cancer therapy. Cancers, 15(3), 982, 2023 |
Resumo(s): | Proliferating 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. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/82536 |
DOI: | 10.3390/cancers15030982 |
ISSN: | 2072-6694 |
Versão da editora: | https://www.mdpi.com/2072-6694/15/3/982/html |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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document_56063_1.pdf | 6,1 MB | Adobe PDF | Ver/Abrir |