Cisplatin-Resistant Urothelial Bladder Cancer Cells Undergo Metabolic Reprogramming beyond the Warburg Effect

Registro completo de metadados
MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversity of Minho-
Autor(es): dc.contributorICVS/3B’s—PT Government Associate Laboratory-
Autor(es): dc.contributorUniversity of Porto-
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.creatorBarbosa-Matos, Catarina-
Autor(es): dc.creatorSilvestre, Ricardo-
Autor(es): dc.creatorPereira-Vieira, Joana-
Autor(es): dc.creatorGonçalves, Samuel Martins-
Autor(es): dc.creatorMendes-Alves, Camille-
Autor(es): dc.creatorParpot, Pier-
Autor(es): dc.creatorPinto, Joana-
Autor(es): dc.creatorCarapito, Ângela-
Autor(es): dc.creatorGuedes de Pinho, Paula-
Autor(es): dc.creatorSantos, Lúcio-
Autor(es): dc.creatorLongatto-Filho, Adhemar-
Autor(es): dc.creatorBaltazar, Fátima-
Data de aceite: dc.date.accessioned2025-08-21T17:30:45Z-
Data de disponibilização: dc.date.available2025-08-21T17:30:45Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2024-04-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/cancers16071418-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/301000-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/301000-
Descrição: dc.descriptionAdvanced urothelial bladder cancer (UBC) patients are tagged by a dismal prognosis and high mortality rates, mostly due to their poor response to standard-of-care platinum-based therapy. Mediators of chemoresistance are not fully elucidated. This work aimed to study the metabolic profile of advanced UBC, in the context of cisplatin resistance. Three isogenic pairs of parental cell lines (T24, HT1376 and KU1919) and the matching cisplatin-resistant (R) sublines were used. A set of functional assays was used to perform a metabolic screening on the cells. In comparison to the parental sublines, a tendency was observed towards an exacerbated glycolytic metabolism in the cisplatin-resistant T24 and HT1376 cells; this glycolytic phenotype was particularly evident for the HT1376/HT1376R pair, for which the cisplatin resistance ratio was higher. HT1376R cells showed decreased basal respiration and oxygen consumption associated with ATP production; in accordance, the extracellular acidification rate was also higher in the resistant subline. Glycolytic rate assay confirmed that these cells presented higher basal glycolysis, with an increase in proton efflux. While the results of real-time metabolomics seem to substantiate the manifestation of the Warburg phenotype in HT1376R cells, a shift towards distinct metabolic pathways involving lactate uptake, lipid biosynthesis and glutamate metabolism occurred with time. On the other hand, KU1919R cells seem to engage in a metabolic rewiring, recovering their preference for oxidative phosphorylation. In conclusion, cisplatin-resistant UBC cells seem to display deep metabolic alterations surpassing the Warburg effect, which likely depend on the molecular signature of each cell line.-
Descrição: dc.descriptionLife and Health Sciences Research Institute (ICVS) Campus de Gualtar University of Minho-
Descrição: dc.descriptionICVS/3B’s—PT Government Associate Laboratory-
Descrição: dc.descriptionCQUM Centre of Chemistry Chemistry Department Campus de Gualtar University of Minho-
Descrição: dc.descriptionCEB—Centre of Biological Engineering Campus de Gualtar University of Minho-
Descrição: dc.descriptionAssociate Laboratory i4HB—Institute for Health and Bioeconomy University of Porto-
Descrição: dc.descriptionUCIBIO—Applied Molecular Biosciences Unit Laboratory of Toxicology Faculty of Pharmacy University of Porto-
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-
Idioma: dc.languageen-
Relação: dc.relationCancers-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectcisplatin resistance-
Palavras-chave: dc.subjectglucose-
Palavras-chave: dc.subjectglutamate-
Palavras-chave: dc.subjectlactate-
Palavras-chave: dc.subjectlipid metabolism-
Palavras-chave: dc.subjecturothelial bladder cancer-
Palavras-chave: dc.subjectWarburg effect-
Título: dc.titleCisplatin-Resistant Urothelial Bladder Cancer Cells Undergo Metabolic Reprogramming beyond the Warburg Effect-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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