Monocarboxylate transporter 1 (MCT1), a tool to stratify acute myeloid leukemia (AML) patients and a vehicle to kill cancer cells
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://doi.org/10.18632/oncotarget.20294 |
Resumo: | The authors thank to Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG,EPE), Liga Portuguesa Contra o Cancro (Terry Fox Project 2011) and Fundação para a Ciência e Tecnologia (PTDC\BIM-ONC\1242\2012) for funding the project. The NMR spectrometers are part of the National NMR Facility supported by Fundação para a Ciência e a Tecnologia (RECI/BBB-BQB/0230/2012). Luis Gonçalves benefited from a fellowship from Fundação para a Ciência e a Tecnologia (SFRH/BPD/111100/2015). The authors acknowledge to Joana Sousa and Sofia Nunes for technical support respectively in NMR and statistics. Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) funded by FEDER funds through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI). iNOVA4Health - UID/Multi/04462/2013, a program financially supported by Fundação para a Ciência e Tecnologia / Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement is acknowledged. |
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Monocarboxylate transporter 1 (MCT1), a tool to stratify acute myeloid leukemia (AML) patients and a vehicle to kill cancer cellsBM microenvironmentLactateMCT1Metabolic switchVEGFSDG 3 - Good Health and Well-beingThe authors thank to Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG,EPE), Liga Portuguesa Contra o Cancro (Terry Fox Project 2011) and Fundação para a Ciência e Tecnologia (PTDC\BIM-ONC\1242\2012) for funding the project. The NMR spectrometers are part of the National NMR Facility supported by Fundação para a Ciência e a Tecnologia (RECI/BBB-BQB/0230/2012). Luis Gonçalves benefited from a fellowship from Fundação para a Ciência e a Tecnologia (SFRH/BPD/111100/2015). The authors acknowledge to Joana Sousa and Sofia Nunes for technical support respectively in NMR and statistics. Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) funded by FEDER funds through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI). iNOVA4Health - UID/Multi/04462/2013, a program financially supported by Fundação para a Ciência e Tecnologia / Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement is acknowledged.Dysregulation of glucose/lactate dynamics plays a role in cancer progression, and MCTs are key elements in metabolic remodeling. VEGF is a relevant growth factor in the maintenance of bone marrow microenvironment and it is also important in hematological diseases. Our aim was to investigate the role of VEGF in the metabolic adaptation of Acute myeloid leukemia (AML) cells by evaluating the metabolic profiles and cell features according to the AML lineage and testing lactate as a metabolic coin. Our in vitro results showed that AML promyelocytic (HL60) and monocytic (THP1) (but not erythroid- HEL) lineages are well adapted to VEGF and lactate rich environment. Their metabolic adaptation relies on high rates of glycolysis to generate intermediates for PPP to support cell proliferation, and on the consumption of glycolysis-generated lactate to supply biomass and energy production. VEGF orchestrates this metabolic network by regulating MCT1 expression. Bromopyruvic acid (BPA) was proven to be an effective cytotoxic in AML, possibly transported by MCT1. Our study reinforces that targeting metabolism can be a good strategy to fight cancer. MCT1 expression at the time of diagnosis can assist on the identification of AML patients that will benefit from BPA therapy. Additionally, MCT1 can be used in targeted delivery of conventional cytotoxic drugs. © Lopes-Coelho et al.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)Instituto de Tecnologia Química e Biológica António Xavier (ITQB)RUNLopes-Coelho, F.Nunes, C.Gouveia-Fernandes, S.Rosas, RitaSilva, F.Gameiro, P.Carvalho, T.da Silva, M.G.Cabeçadas, J.Dias, S.Gonçalves, L.G.Serpa, J.2017-10-20T22:03:00Z20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article21application/pdfhttps://doi.org/10.18632/oncotarget.20294eng1949-2553PURE: 3225951https://www.scopus.com/inward/record.uri?eid=2-s2.0-85030846809&doi=10.18632%2foncotarget.20294&partnerID=40&md5=87d7ac838f8600623a08362fe4ab9917https://doi.org/10.18632/oncotarget.20294info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:12:37Zoai:run.unl.pt:10362/24377Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:28:02.218679Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Monocarboxylate transporter 1 (MCT1), a tool to stratify acute myeloid leukemia (AML) patients and a vehicle to kill cancer cells |
title |
Monocarboxylate transporter 1 (MCT1), a tool to stratify acute myeloid leukemia (AML) patients and a vehicle to kill cancer cells |
spellingShingle |
Monocarboxylate transporter 1 (MCT1), a tool to stratify acute myeloid leukemia (AML) patients and a vehicle to kill cancer cells Lopes-Coelho, F. BM microenvironment Lactate MCT1 Metabolic switch VEGF SDG 3 - Good Health and Well-being |
title_short |
Monocarboxylate transporter 1 (MCT1), a tool to stratify acute myeloid leukemia (AML) patients and a vehicle to kill cancer cells |
title_full |
Monocarboxylate transporter 1 (MCT1), a tool to stratify acute myeloid leukemia (AML) patients and a vehicle to kill cancer cells |
title_fullStr |
Monocarboxylate transporter 1 (MCT1), a tool to stratify acute myeloid leukemia (AML) patients and a vehicle to kill cancer cells |
title_full_unstemmed |
Monocarboxylate transporter 1 (MCT1), a tool to stratify acute myeloid leukemia (AML) patients and a vehicle to kill cancer cells |
title_sort |
Monocarboxylate transporter 1 (MCT1), a tool to stratify acute myeloid leukemia (AML) patients and a vehicle to kill cancer cells |
author |
Lopes-Coelho, F. |
author_facet |
Lopes-Coelho, F. Nunes, C. Gouveia-Fernandes, S. Rosas, Rita Silva, F. Gameiro, P. Carvalho, T. da Silva, M.G. Cabeçadas, J. Dias, S. Gonçalves, L.G. Serpa, J. |
author_role |
author |
author2 |
Nunes, C. Gouveia-Fernandes, S. Rosas, Rita Silva, F. Gameiro, P. Carvalho, T. da Silva, M.G. Cabeçadas, J. Dias, S. Gonçalves, L.G. Serpa, J. |
author2_role |
author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) Centro de Estudos de Doenças Crónicas (CEDOC) Instituto de Tecnologia Química e Biológica António Xavier (ITQB) RUN |
dc.contributor.author.fl_str_mv |
Lopes-Coelho, F. Nunes, C. Gouveia-Fernandes, S. Rosas, Rita Silva, F. Gameiro, P. Carvalho, T. da Silva, M.G. Cabeçadas, J. Dias, S. Gonçalves, L.G. Serpa, J. |
dc.subject.por.fl_str_mv |
BM microenvironment Lactate MCT1 Metabolic switch VEGF SDG 3 - Good Health and Well-being |
topic |
BM microenvironment Lactate MCT1 Metabolic switch VEGF SDG 3 - Good Health and Well-being |
description |
The authors thank to Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG,EPE), Liga Portuguesa Contra o Cancro (Terry Fox Project 2011) and Fundação para a Ciência e Tecnologia (PTDC\BIM-ONC\1242\2012) for funding the project. The NMR spectrometers are part of the National NMR Facility supported by Fundação para a Ciência e a Tecnologia (RECI/BBB-BQB/0230/2012). Luis Gonçalves benefited from a fellowship from Fundação para a Ciência e a Tecnologia (SFRH/BPD/111100/2015). The authors acknowledge to Joana Sousa and Sofia Nunes for technical support respectively in NMR and statistics. Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) funded by FEDER funds through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI). iNOVA4Health - UID/Multi/04462/2013, a program financially supported by Fundação para a Ciência e Tecnologia / Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement is acknowledged. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-10-20T22:03:00Z 2017 2017-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://doi.org/10.18632/oncotarget.20294 |
url |
https://doi.org/10.18632/oncotarget.20294 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1949-2553 PURE: 3225951 https://www.scopus.com/inward/record.uri?eid=2-s2.0-85030846809&doi=10.18632%2foncotarget.20294&partnerID=40&md5=87d7ac838f8600623a08362fe4ab9917 https://doi.org/10.18632/oncotarget.20294 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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21 application/pdf |
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