Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/58061 |
Resumo: | Acute myeloid leukaemia (AML) comprises a heterogeneous group of hematologic neoplasms characterized by diverse combinations of genetic, phenotypic and clinical features representing a major challenge for the development of targeted therapies. Metabolic reprogramming, mainly driven by deregulation of the nutrient-sensing pathways as AMPK, mTOR and PI3K/AKT, has been associated with cancer cells, including AML cells, survival and proliferation. Nevertheless, the role of these metabolic adaptations on the AML pathogenesis is still controversial. In this work, the metabolic status and the respective metabolic networks operating in different AML cells (NB-4, HL-60 and KG-1) and their impact on autophagy and survival was characterized. Data show that whereas KG-1 cells exhibited preferential mitochondrial oxidative phosphorylation metabolism with constitutive co-activation of AMPK and mTORC1 associated with increased autophagy, NB-4 and HL-60 cells displayed a dependent glycolytic profile mainly associated with AKT/mTORC1 activation and low autophagy flux. Inhibition of AKT is disclosed as a promising therapeutical target in some scenarios while inhibition of AMPK and mTORC1 has no major impact on KG-1 cells' survival. The results highlight an exclusive metabolic profile for each tested AML cells and its impact on determination of the anti-leukaemia efficacy and on personalized combinatory therapy with conventional and targeted agents. |
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Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cellsacute myeloid leukaemiaautophagyenergetic metabolismglycolysismitochondrial oxidative phosphorylationnutrient-sensing pathwaysCiências Médicas::Medicina BásicaScience & TechnologyAcute myeloid leukaemia (AML) comprises a heterogeneous group of hematologic neoplasms characterized by diverse combinations of genetic, phenotypic and clinical features representing a major challenge for the development of targeted therapies. Metabolic reprogramming, mainly driven by deregulation of the nutrient-sensing pathways as AMPK, mTOR and PI3K/AKT, has been associated with cancer cells, including AML cells, survival and proliferation. Nevertheless, the role of these metabolic adaptations on the AML pathogenesis is still controversial. In this work, the metabolic status and the respective metabolic networks operating in different AML cells (NB-4, HL-60 and KG-1) and their impact on autophagy and survival was characterized. Data show that whereas KG-1 cells exhibited preferential mitochondrial oxidative phosphorylation metabolism with constitutive co-activation of AMPK and mTORC1 associated with increased autophagy, NB-4 and HL-60 cells displayed a dependent glycolytic profile mainly associated with AKT/mTORC1 activation and low autophagy flux. Inhibition of AKT is disclosed as a promising therapeutical target in some scenarios while inhibition of AMPK and mTORC1 has no major impact on KG-1 cells' survival. The results highlight an exclusive metabolic profile for each tested AML cells and its impact on determination of the anti-leukaemia efficacy and on personalized combinatory therapy with conventional and targeted agents.This work was developed under the scope of the project NORTE‐01‐0145‐FEDER‐000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and by FEDER, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI‐01‐0145‐FEDER‐007038. OP and BSM are supported by fellowships from the Fundação para a Ciência e Tecnologia (FCT, Portugal) (SFRH/BD/52292/2013 and SFRH/BPD/90533/2012, respectively)info:eu-repo/semantics/publishedVersionBlackwell Publishing Inc.Universidade do MinhoPereira, OlgaTeixeira, AlexandraMarques, Maria Belém Sousa SampaioCastro, IsabelGirão, HenriqueLudovico, Paula2018-102018-10-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/58061engPereira O, Teixeira A, Sampaio-Marques B, Castro I, Gir ~ ao H, Ludovico P. Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells. J Cell Mol Med . 2018;22:4807 – 4817. https://doi.org/10.1111/jcmm.137371582-18381582-493410.1111/jcmm.1373730117681https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.13737info: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:RCAAP2023-07-21T12:13:46Zoai:repositorium.sdum.uminho.pt:1822/58061Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:05:56.346025Repositório 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 |
Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells |
title |
Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells |
spellingShingle |
Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells Pereira, Olga acute myeloid leukaemia autophagy energetic metabolism glycolysis mitochondrial oxidative phosphorylation nutrient-sensing pathways Ciências Médicas::Medicina Básica Science & Technology |
title_short |
Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells |
title_full |
Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells |
title_fullStr |
Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells |
title_full_unstemmed |
Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells |
title_sort |
Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells |
author |
Pereira, Olga |
author_facet |
Pereira, Olga Teixeira, Alexandra Marques, Maria Belém Sousa Sampaio Castro, Isabel Girão, Henrique Ludovico, Paula |
author_role |
author |
author2 |
Teixeira, Alexandra Marques, Maria Belém Sousa Sampaio Castro, Isabel Girão, Henrique Ludovico, Paula |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Pereira, Olga Teixeira, Alexandra Marques, Maria Belém Sousa Sampaio Castro, Isabel Girão, Henrique Ludovico, Paula |
dc.subject.por.fl_str_mv |
acute myeloid leukaemia autophagy energetic metabolism glycolysis mitochondrial oxidative phosphorylation nutrient-sensing pathways Ciências Médicas::Medicina Básica Science & Technology |
topic |
acute myeloid leukaemia autophagy energetic metabolism glycolysis mitochondrial oxidative phosphorylation nutrient-sensing pathways Ciências Médicas::Medicina Básica Science & Technology |
description |
Acute myeloid leukaemia (AML) comprises a heterogeneous group of hematologic neoplasms characterized by diverse combinations of genetic, phenotypic and clinical features representing a major challenge for the development of targeted therapies. Metabolic reprogramming, mainly driven by deregulation of the nutrient-sensing pathways as AMPK, mTOR and PI3K/AKT, has been associated with cancer cells, including AML cells, survival and proliferation. Nevertheless, the role of these metabolic adaptations on the AML pathogenesis is still controversial. In this work, the metabolic status and the respective metabolic networks operating in different AML cells (NB-4, HL-60 and KG-1) and their impact on autophagy and survival was characterized. Data show that whereas KG-1 cells exhibited preferential mitochondrial oxidative phosphorylation metabolism with constitutive co-activation of AMPK and mTORC1 associated with increased autophagy, NB-4 and HL-60 cells displayed a dependent glycolytic profile mainly associated with AKT/mTORC1 activation and low autophagy flux. Inhibition of AKT is disclosed as a promising therapeutical target in some scenarios while inhibition of AMPK and mTORC1 has no major impact on KG-1 cells' survival. The results highlight an exclusive metabolic profile for each tested AML cells and its impact on determination of the anti-leukaemia efficacy and on personalized combinatory therapy with conventional and targeted agents. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-10 2018-10-01T00:00:00Z |
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 |
http://hdl.handle.net/1822/58061 |
url |
http://hdl.handle.net/1822/58061 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Pereira O, Teixeira A, Sampaio-Marques B, Castro I, Gir ~ ao H, Ludovico P. Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells. J Cell Mol Med . 2018;22:4807 – 4817. https://doi.org/10.1111/jcmm.13737 1582-1838 1582-4934 10.1111/jcmm.13737 30117681 https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.13737 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Blackwell Publishing Inc. |
publisher.none.fl_str_mv |
Blackwell Publishing Inc. |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799132472913428480 |