Cysteine and Folate metabolism are targetable vulnerabilities of metastatic colorectal cancer

With most cancer-related deaths resulting from metastasis, the development of new therapeutic approaches against metastatic colorectal cancer (mCRC) is essential to increasing patient survival. The metabolic adaptations that support mCRC remain undefined and their elucidation is crucial to identify...

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Autores: Tarragó-Celada, Josep, Foguet Coll, Carles, Tarrado Castellarnau, Míriam Neus, Marín Martínez, Silvia, Hernández-Alias, Xavier, Perarnau, Jordi, Morrish, Fionnuala, Hockenbery, David, Gomis i Cabré, Roger, Ruppin, Eytan, Yuneva, Mariia, Atauri Carulla, Ramón de, Cascante i Serratosa, Marta
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/175317
Acceso en línea:https://hdl.handle.net/2445/175317
Access Level:acceso abierto
Palabra clave:Càncer colorectal
Metàstasi
Metabolisme
Colorectal cancer
Metastasis
Metabolism
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spelling Cysteine and Folate metabolism are targetable vulnerabilities of metastatic colorectal cancerTarragó-Celada, JosepFoguet Coll, CarlesTarrado Castellarnau, Míriam NeusMarín Martínez, SilviaHernández-Alias, XavierPerarnau, JordiMorrish, FionnualaHockenbery, DavidGomis i Cabré, RogerRuppin, EytanYuneva, MariiaAtauri Carulla, Ramón deCascante i Serratosa, MartaCàncer colorectalMetàstasiMetabolismeColorectal cancerMetastasisMetabolismWith most cancer-related deaths resulting from metastasis, the development of new therapeutic approaches against metastatic colorectal cancer (mCRC) is essential to increasing patient survival. The metabolic adaptations that support mCRC remain undefined and their elucidation is crucial to identify potential therapeutic targets. Here, we employed a strategy for the rational identification of targetable metabolic vulnerabilities. This strategy involved first a thorough metabolic characterisation of same-patient-derived cell lines from primary colon adenocarcinoma (SW480), its lymph node metastasis (SW620) and a liver metastatic derivative (SW620-LiM2), and second, using a novel multi-omics integration workflow, identification of metabolic vulnerabilities specific to the metastatic cell lines. We discovered that the metastatic cell lines are selectively vulnerable to the inhibition of cystine import and folate metabolism, two key pathways in redox homeostasis. Specifically, we identified the system xCT and MTHFD1 genes as potential therapeutic targets, both individually and combined, for combating mCRC.MDPI2021202120212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion22 p.application/pdfhttps://hdl.handle.net/2445/175317Articles publicats en revistes (Bioquímica i Biomedicina Molecular)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3390/cancers13030425Cancers, 2021, vol. 13, num. 3, p. 425https://doi.org/10.3390/cancers13030425cc-by (c) Tarragó-Celada, Josep et al., 2021http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1753172026-05-29T05:05:01Z
dc.title.none.fl_str_mv Cysteine and Folate metabolism are targetable vulnerabilities of metastatic colorectal cancer
title Cysteine and Folate metabolism are targetable vulnerabilities of metastatic colorectal cancer
spellingShingle Cysteine and Folate metabolism are targetable vulnerabilities of metastatic colorectal cancer
Tarragó-Celada, Josep
Càncer colorectal
Metàstasi
Metabolisme
Colorectal cancer
Metastasis
Metabolism
title_short Cysteine and Folate metabolism are targetable vulnerabilities of metastatic colorectal cancer
title_full Cysteine and Folate metabolism are targetable vulnerabilities of metastatic colorectal cancer
title_fullStr Cysteine and Folate metabolism are targetable vulnerabilities of metastatic colorectal cancer
title_full_unstemmed Cysteine and Folate metabolism are targetable vulnerabilities of metastatic colorectal cancer
title_sort Cysteine and Folate metabolism are targetable vulnerabilities of metastatic colorectal cancer
dc.creator.none.fl_str_mv Tarragó-Celada, Josep
Foguet Coll, Carles
Tarrado Castellarnau, Míriam Neus
Marín Martínez, Silvia
Hernández-Alias, Xavier
Perarnau, Jordi
Morrish, Fionnuala
Hockenbery, David
Gomis i Cabré, Roger
Ruppin, Eytan
Yuneva, Mariia
Atauri Carulla, Ramón de
Cascante i Serratosa, Marta
author Tarragó-Celada, Josep
author_facet Tarragó-Celada, Josep
Foguet Coll, Carles
Tarrado Castellarnau, Míriam Neus
Marín Martínez, Silvia
Hernández-Alias, Xavier
Perarnau, Jordi
Morrish, Fionnuala
Hockenbery, David
Gomis i Cabré, Roger
Ruppin, Eytan
Yuneva, Mariia
Atauri Carulla, Ramón de
Cascante i Serratosa, Marta
author_role author
author2 Foguet Coll, Carles
Tarrado Castellarnau, Míriam Neus
Marín Martínez, Silvia
Hernández-Alias, Xavier
Perarnau, Jordi
Morrish, Fionnuala
Hockenbery, David
Gomis i Cabré, Roger
Ruppin, Eytan
Yuneva, Mariia
Atauri Carulla, Ramón de
Cascante i Serratosa, Marta
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer colorectal
Metàstasi
Metabolisme
Colorectal cancer
Metastasis
Metabolism
topic Càncer colorectal
Metàstasi
Metabolisme
Colorectal cancer
Metastasis
Metabolism
description With most cancer-related deaths resulting from metastasis, the development of new therapeutic approaches against metastatic colorectal cancer (mCRC) is essential to increasing patient survival. The metabolic adaptations that support mCRC remain undefined and their elucidation is crucial to identify potential therapeutic targets. Here, we employed a strategy for the rational identification of targetable metabolic vulnerabilities. This strategy involved first a thorough metabolic characterisation of same-patient-derived cell lines from primary colon adenocarcinoma (SW480), its lymph node metastasis (SW620) and a liver metastatic derivative (SW620-LiM2), and second, using a novel multi-omics integration workflow, identification of metabolic vulnerabilities specific to the metastatic cell lines. We discovered that the metastatic cell lines are selectively vulnerable to the inhibition of cystine import and folate metabolism, two key pathways in redox homeostasis. Specifically, we identified the system xCT and MTHFD1 genes as potential therapeutic targets, both individually and combined, for combating mCRC.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/175317
url https://hdl.handle.net/2445/175317
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/cancers13030425
Cancers, 2021, vol. 13, num. 3, p. 425
https://doi.org/10.3390/cancers13030425
dc.rights.none.fl_str_mv cc-by (c) Tarragó-Celada, Josep et al., 2021
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Tarragó-Celada, Josep et al., 2021
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 22 p.
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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