Publicação
Cisplatin-resistant urothelial bladder cancer cells undergo metabolic reprogramming beyond the Warburg effect
| Resumo: | Advanced 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. |
|---|---|
| Autores principais: | Afonso, Julieta Alexandra Pereira |
| Outros Autores: | Matos, Ana Catarina Barbosa; Silvestre, Ricardo Jorge Leal; Pereira-Vieira, Joana; Gonçalves, Samuel Martins; Mendes-Alves, Camille; Parpot, Pier; Pinto, Joana; Carapito, Ângela; Guedes de Pinho, Paula; Santos, Lúcio; Longatto-Filho, Adhemar; Baltazar, Fátima |
| Assunto: | Urothelial bladder cancer Cisplatin resistance Warburg effect Glucose Lactate Lipid metabolism Glutamate |
| Ano: | 2024 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1866877665056653312 |
|---|---|
| author | Afonso, Julieta Alexandra Pereira |
| author2 | Matos, Ana Catarina Barbosa Silvestre, Ricardo Jorge Leal Pereira-Vieira, Joana Gonçalves, Samuel Martins Mendes-Alves, Camille Parpot, Pier Pinto, Joana Carapito, Ângela Guedes de Pinho, Paula Santos, Lúcio Longatto-Filho, Adhemar Baltazar, Fátima |
| author2_role | author author author author author author author author author author author author |
| author_facet | Afonso, Julieta Alexandra Pereira Matos, Ana Catarina Barbosa Silvestre, Ricardo Jorge Leal Pereira-Vieira, Joana Gonçalves, Samuel Martins Mendes-Alves, Camille Parpot, Pier Pinto, Joana Carapito, Ângela Guedes de Pinho, Paula Santos, Lúcio Longatto-Filho, Adhemar Baltazar, Fátima |
| author_role | author |
| contributor_name_str_mv | Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Afonso, Julieta Alexandra Pereira\"},{\"Person.name\":\"Matos, Ana Catarina Barbosa\"},{\"Person.name\":\"Silvestre, Ricardo Jorge Leal\"},{\"Person.name\":\"Pereira-Vieira, Joana\"},{\"Person.name\":\"Gonçalves, Samuel Martins\"},{\"Person.name\":\"Mendes-Alves, Camille\"},{\"Person.name\":\"Parpot, Pier\"},{\"Person.name\":\"Pinto, Joana\"},{\"Person.name\":\"Carapito, Ângela\"},{\"Person.name\":\"Guedes de Pinho, Paula\"},{\"Person.name\":\"Santos, Lúcio\"},{\"Person.name\":\"Longatto-Filho, Adhemar\"},{\"Person.name\":\"Baltazar, Fátima\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Afonso, Julieta Alexandra Pereira Matos, Ana Catarina Barbosa Silvestre, Ricardo Jorge Leal Pereira-Vieira, Joana Gonçalves, Samuel Martins Mendes-Alves, Camille Parpot, Pier Pinto, Joana Carapito, Ângela Guedes de Pinho, Paula Santos, Lúcio Longatto-Filho, Adhemar Baltazar, Fátima |
| datacite.date.Accepted.fl_str_mv | 2024-04-05T00:00:00Z |
| datacite.date.available.fl_str_mv | 2024-05-31T14:16:02Z |
| datacite.date.embargoed.fl_str_mv | 2024-05-31T14:16:02Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Urothelial bladder cancer Cisplatin resistance Warburg effect Glucose Lactate Lipid metabolism Glutamate |
| datacite.titles.title.fl_str_mv | Cisplatin-resistant urothelial bladder cancer cells undergo metabolic reprogramming beyond the Warburg effect |
| dc.contributor.none.fl_str_mv | Universidade do Minho |
| dc.creator.none.fl_str_mv | Afonso, Julieta Alexandra Pereira Matos, Ana Catarina Barbosa Silvestre, Ricardo Jorge Leal Pereira-Vieira, Joana Gonçalves, Samuel Martins Mendes-Alves, Camille Parpot, Pier Pinto, Joana Carapito, Ângela Guedes de Pinho, Paula Santos, Lúcio Longatto-Filho, Adhemar Baltazar, Fátima |
| dc.date.Accepted.fl_str_mv | 2024-04-05T00:00:00Z |
| dc.date.available.fl_str_mv | 2024-05-31T14:16:02Z |
| dc.date.embargoed.fl_str_mv | 2024-05-31T14:16:02Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/91633 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Multidisciplinary Digital Publishing Institute (MDPI) |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Urothelial bladder cancer Cisplatin resistance Warburg effect Glucose Lactate Lipid metabolism Glutamate |
| dc.title.fl_str_mv | Cisplatin-resistant urothelial bladder cancer cells undergo metabolic reprogramming beyond the Warburg effect |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Advanced 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorium.uminho.pt/bitstreams/ff0558b7-a5b2-4700-bfb4-df43fe419be6/download |
| id | rum_e4e2b5a52e29b0578d050e2f98c4cd12 |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/91633 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/91633 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Afonso, Julieta Alexandra Pereira Matos, Ana Catarina Barbosa Silvestre, Ricardo Jorge Leal Pereira-Vieira, Joana Gonçalves, Samuel Martins Mendes-Alves, Camille Parpot, Pier Pinto, Joana Carapito, Ângela Guedes de Pinho, Paula Santos, Lúcio Longatto-Filho, Adhemar Baltazar, Fátima |
| publishDate | 2024 |
| publisher.none.fl_str_mv | Multidisciplinary Digital Publishing Institute (MDPI) |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engMultidisciplinary Digital Publishing Institute (MDPI)porAdvanced 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.application/pdfporCisplatin-resistant urothelial bladder cancer cells undergo metabolic reprogramming beyond the Warburg effectAfonso, Julieta Alexandra PereiraMatos, Ana Catarina BarbosaSilvestre, Ricardo Jorge LealPereira-Vieira, JoanaGonçalves, Samuel MartinsMendes-Alves, CamilleParpot, PierPinto, JoanaCarapito, ÂngelaGuedes de Pinho, PaulaSantos, LúcioLongatto-Filho, AdhemarBaltazar, FátimaHostingInstitutionOrganizationalUniversidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptISSNIsPartOf2072-6694DOIIsPartOf10.3390/cancers160714182024-05-31T14:16:02Z2024-04-052024-05-14T19:15:58Z2024-04-05T00:00:00ZHandlehttps://hdl.handle.net/1822/91633http://purl.org/coar/access_right/c_abf2open accessUrothelial bladder cancerCisplatin resistanceWarburg effectGlucoseLactateLipid metabolismGlutamate5543109 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorium.uminho.pt/bitstreams/ff0558b7-a5b2-4700-bfb4-df43fe419be6/download |
| spellingShingle | Cisplatin-resistant urothelial bladder cancer cells undergo metabolic reprogramming beyond the Warburg effect Afonso, Julieta Alexandra Pereira Urothelial bladder cancer Cisplatin resistance Warburg effect Glucose Lactate Lipid metabolism Glutamate |
| status | SINGLETON |
| subject.fl_str_mv | Urothelial bladder cancer Cisplatin resistance Warburg effect Glucose Lactate Lipid metabolism Glutamate |
| title | Cisplatin-resistant urothelial bladder cancer cells undergo metabolic reprogramming beyond the Warburg effect |
| title_full | Cisplatin-resistant urothelial bladder cancer cells undergo metabolic reprogramming beyond the Warburg effect |
| title_fullStr | Cisplatin-resistant urothelial bladder cancer cells undergo metabolic reprogramming beyond the Warburg effect |
| title_full_unstemmed | Cisplatin-resistant urothelial bladder cancer cells undergo metabolic reprogramming beyond the Warburg effect |
| title_short | Cisplatin-resistant urothelial bladder cancer cells undergo metabolic reprogramming beyond the Warburg effect |
| title_sort | Cisplatin-resistant urothelial bladder cancer cells undergo metabolic reprogramming beyond the Warburg effect |
| topic | Urothelial bladder cancer Cisplatin resistance Warburg effect Glucose Lactate Lipid metabolism Glutamate |
| topic_facet | Urothelial bladder cancer Cisplatin resistance Warburg effect Glucose Lactate Lipid metabolism Glutamate |
| url | https://hdl.handle.net/1822/91633 |
| visible | 1 |