Cysteine Boosts Fitness Under Hypoxia-Mimicked Conditions in Ovarian Cancer by Metabolic Reprogramming

Detalhes bibliográficos
Autor(a) principal: Nunes, Sofia C.
Data de Publicação: 2021
Outros Autores: Ramos, Cristiano, Santos, Inês, Mendes, Cindy, Silva, Fernanda, Vicente, João B., Pereira, Sofia A., Félix, Ana, Gonçalves, Luís G., Serpa, Jacinta
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/125092
Resumo: Funding Information: Funding. This research was supported by Funda??o para a Ci?ncia e Tecnologia (FCT) (Ph.D. ProRegeM program, Ref: PD/BD/105893/2014; FCT individual Ph.D. fellowship Ref: 2020.06956.BD) and iNOVA4 Health (Project 4 and Project 21). iNOVA4Health-UID/Multi/04462/2013 is a program financially supported by Funda??o para a Ci?ncia e Tecnologia/ Minist?rio da Educa??o e Ci?ncia, through national funds. The authors would like to acknowledge the Instituto Portugu?s de Oncologia de Lisboa Francisco Gentil (IPOLFG) for partially funding the project. Publisher Copyright: © Copyright © 2021 Nunes, Ramos, Santos, Mendes, Silva, Vicente, Pereira, Félix, Gonçalves and Serpa.
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spelling Cysteine Boosts Fitness Under Hypoxia-Mimicked Conditions in Ovarian Cancer by Metabolic Reprogrammingbioenergeticscarbon sourcecysteinecystinehydrogen sulfidehypoxiamicroenvironmentovarian cancerDevelopmental BiologyCell BiologySDG 3 - Good Health and Well-beingFunding Information: Funding. This research was supported by Funda??o para a Ci?ncia e Tecnologia (FCT) (Ph.D. ProRegeM program, Ref: PD/BD/105893/2014; FCT individual Ph.D. fellowship Ref: 2020.06956.BD) and iNOVA4 Health (Project 4 and Project 21). iNOVA4Health-UID/Multi/04462/2013 is a program financially supported by Funda??o para a Ci?ncia e Tecnologia/ Minist?rio da Educa??o e Ci?ncia, through national funds. The authors would like to acknowledge the Instituto Portugu?s de Oncologia de Lisboa Francisco Gentil (IPOLFG) for partially funding the project. Publisher Copyright: © Copyright © 2021 Nunes, Ramos, Santos, Mendes, Silva, Vicente, Pereira, Félix, Gonçalves and Serpa.Among gynecologic malignancies, ovarian cancer is the third most prevalent and the most common cause of death, especially due to diagnosis at an advanced stage together with resistance to therapy. As a solid tumor grows, cancer cells in the microenvironment are exposed to regions of hypoxia, a selective pressure prompting tumor progression and chemoresistance. We have previously shown that cysteine contributes to the adaptation to this hypoxic microenvironment, but the mechanisms by which cysteine protects ovarian cancer cells from hypoxia-induced death are still to be unveiled. Herein, we hypothesized that cysteine contribution relies on cellular metabolism reprogramming and energy production, being cysteine itself a metabolic source. Our results strongly supported a role of xCT symporter in energy production that requires cysteine metabolism instead of hydrogen sulfide (H2S) per se. Cysteine degradation depends on the action of the H2S-synthesizing enzymes cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and/or 3-mercaptopyruvate sulfurtransferase (MpST; together with cysteine aminotransferase, CAT). In normoxia, CBS and CSE inhibition had a mild impact on cysteine-sustained ATP production, pointing out the relevance of CAT + MpST pathway. However, in hypoxia, the concomitant inhibition of CBS and CSE had a stronger impact on ATP synthesis, thus also supporting a role of their hydrogen sulfide and/or cysteine persulfide-synthesizing activity in this stressful condition. However, the relative contributions of each of these enzymes (CBS/CSE/MpST) on cysteine-derived ATP synthesis under hypoxia remains unclear, due to the lack of specific inhibitors. Strikingly, NMR analysis strongly supported a role of cysteine in the whole cellular metabolism rewiring under hypoxia. Additionally, the use of cysteine to supply biosynthesis and bioenergetics was reinforced, bringing cysteine to the plateau of a main carbon sources in cancer. Collectively, this work supports that sulfur and carbon metabolism reprogramming underlies the adaptation to hypoxic microenvironment promoted by cysteine in ovarian cancer.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Instituto de Tecnologia Química e Biológica António Xavier (ITQB)RUNNunes, Sofia C.Ramos, CristianoSantos, InêsMendes, CindySilva, FernandaVicente, João B.Pereira, Sofia A.Félix, AnaGonçalves, Luís G.Serpa, Jacinta2021-09-24T02:24:57Z2021-08-112021-08-11T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/125092eng2296-634XPURE: 33520957https://doi.org/10.3389/fcell.2021.722412info: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:RCAAP2024-03-11T05:06:17Zoai:run.unl.pt:10362/125092Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:45:39.580357Repositório 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 Cysteine Boosts Fitness Under Hypoxia-Mimicked Conditions in Ovarian Cancer by Metabolic Reprogramming
title Cysteine Boosts Fitness Under Hypoxia-Mimicked Conditions in Ovarian Cancer by Metabolic Reprogramming
spellingShingle Cysteine Boosts Fitness Under Hypoxia-Mimicked Conditions in Ovarian Cancer by Metabolic Reprogramming
Nunes, Sofia C.
bioenergetics
carbon source
cysteine
cystine
hydrogen sulfide
hypoxia
microenvironment
ovarian cancer
Developmental Biology
Cell Biology
SDG 3 - Good Health and Well-being
title_short Cysteine Boosts Fitness Under Hypoxia-Mimicked Conditions in Ovarian Cancer by Metabolic Reprogramming
title_full Cysteine Boosts Fitness Under Hypoxia-Mimicked Conditions in Ovarian Cancer by Metabolic Reprogramming
title_fullStr Cysteine Boosts Fitness Under Hypoxia-Mimicked Conditions in Ovarian Cancer by Metabolic Reprogramming
title_full_unstemmed Cysteine Boosts Fitness Under Hypoxia-Mimicked Conditions in Ovarian Cancer by Metabolic Reprogramming
title_sort Cysteine Boosts Fitness Under Hypoxia-Mimicked Conditions in Ovarian Cancer by Metabolic Reprogramming
author Nunes, Sofia C.
author_facet Nunes, Sofia C.
Ramos, Cristiano
Santos, Inês
Mendes, Cindy
Silva, Fernanda
Vicente, João B.
Pereira, Sofia A.
Félix, Ana
Gonçalves, Luís G.
Serpa, Jacinta
author_role author
author2 Ramos, Cristiano
Santos, Inês
Mendes, Cindy
Silva, Fernanda
Vicente, João B.
Pereira, Sofia A.
Félix, Ana
Gonçalves, Luís G.
Serpa, Jacinta
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Centro de Estudos de Doenças Crónicas (CEDOC)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Instituto de Tecnologia Química e Biológica António Xavier (ITQB)
RUN
dc.contributor.author.fl_str_mv Nunes, Sofia C.
Ramos, Cristiano
Santos, Inês
Mendes, Cindy
Silva, Fernanda
Vicente, João B.
Pereira, Sofia A.
Félix, Ana
Gonçalves, Luís G.
Serpa, Jacinta
dc.subject.por.fl_str_mv bioenergetics
carbon source
cysteine
cystine
hydrogen sulfide
hypoxia
microenvironment
ovarian cancer
Developmental Biology
Cell Biology
SDG 3 - Good Health and Well-being
topic bioenergetics
carbon source
cysteine
cystine
hydrogen sulfide
hypoxia
microenvironment
ovarian cancer
Developmental Biology
Cell Biology
SDG 3 - Good Health and Well-being
description Funding Information: Funding. This research was supported by Funda??o para a Ci?ncia e Tecnologia (FCT) (Ph.D. ProRegeM program, Ref: PD/BD/105893/2014; FCT individual Ph.D. fellowship Ref: 2020.06956.BD) and iNOVA4 Health (Project 4 and Project 21). iNOVA4Health-UID/Multi/04462/2013 is a program financially supported by Funda??o para a Ci?ncia e Tecnologia/ Minist?rio da Educa??o e Ci?ncia, through national funds. The authors would like to acknowledge the Instituto Portugu?s de Oncologia de Lisboa Francisco Gentil (IPOLFG) for partially funding the project. Publisher Copyright: © Copyright © 2021 Nunes, Ramos, Santos, Mendes, Silva, Vicente, Pereira, Félix, Gonçalves and Serpa.
publishDate 2021
dc.date.none.fl_str_mv 2021-09-24T02:24:57Z
2021-08-11
2021-08-11T00:00:00Z
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/10362/125092
url http://hdl.handle.net/10362/125092
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2296-634X
PURE: 33520957
https://doi.org/10.3389/fcell.2021.722412
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.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
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