Loss of dyskerin facilitates the acquisition of metastatic traits by altering the mevalonate pathway

The initial dissemination of cancer cells from many primary tumors implies intravasation to lymphatic nodes or blood vessels. To investigate the mechanisms involved, we analyzed the expression of small non-coding RNAs in cutaneous squamous cell carcinoma (cSCC), a prevalent tumor that mainly spreads...

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Autores: Andrades, Evelyn, Toll Abelló, Agustín, Deza, Gustavo, Segura Tigell, Sonia, Gimeno, Ramón, Espadas, Guadalupe, Sabidó Aguadé, Eduard, 1981-, Haro, Noemí, Pozo Mendoza, Óscar J., 1975-, Bódalo-Torruella, Marta, Torres, Paloma, Pujol Vallverdú, Ramón M., Hernández-Muñoz, Inmaculada
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/57244
Acceso en línea:http://hdl.handle.net/10230/57244
http://dx.doi.org/10.26508/lsa.202201692
Access Level:acceso abierto
Palabra clave:Càncer
Sistema limfàtic
Metàstasi limfàtica
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spelling Loss of dyskerin facilitates the acquisition of metastatic traits by altering the mevalonate pathwayAndrades, EvelynToll Abelló, AgustínDeza, GustavoSegura Tigell, SoniaGimeno, RamónEspadas, GuadalupeSabidó Aguadé, Eduard, 1981-Haro, NoemíPozo Mendoza, Óscar J., 1975-Bódalo-Torruella, MartaTorres, PalomaPujol Vallverdú, Ramón M.Hernández-Muñoz, InmaculadaCàncerSistema limfàticMetàstasi limfàticaThe initial dissemination of cancer cells from many primary tumors implies intravasation to lymphatic nodes or blood vessels. To investigate the mechanisms involved, we analyzed the expression of small non-coding RNAs in cutaneous squamous cell carcinoma (cSCC), a prevalent tumor that mainly spreads to lymph nodes. We report the reduced expression of small nucleolar RNAs in primary cSCCs that metastasized when compared to non-metastasizing cSCCs, and the progressive loss of DKC1 (dyskerin, which stabilizes the small nucleolar RNAs) along the metastasis. DKC1 depletion in cSCC cells triggered lipid metabolism by altering the mevalonate pathway and the acquisition of metastatic traits. Treatment of DKC1-depleted cells with simvastatin, an inhibitor of the mevalonate pathway, blocked the expression of proteins involved in the epithelial-to-mesenchymal transition. Consistently, the expression of the enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 1 was associated with pathological features of high metastatic risk in cSCC patients. Our data underpin the relevance of the mevalonate metabolism in metastatic dissemination and pave the possible incorporation of therapeutic approaches among the antineoplastic drugs used in routine patient care.Life Science Alliance LLC202320232023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/57244http://dx.doi.org/10.26508/lsa.202201692reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésLife Science Alliance. 2023 Apr;6(4):e20220169© 2023 Andrades et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/572442026-06-12T07:21:37Z
dc.title.none.fl_str_mv Loss of dyskerin facilitates the acquisition of metastatic traits by altering the mevalonate pathway
title Loss of dyskerin facilitates the acquisition of metastatic traits by altering the mevalonate pathway
spellingShingle Loss of dyskerin facilitates the acquisition of metastatic traits by altering the mevalonate pathway
Andrades, Evelyn
Càncer
Sistema limfàtic
Metàstasi limfàtica
title_short Loss of dyskerin facilitates the acquisition of metastatic traits by altering the mevalonate pathway
title_full Loss of dyskerin facilitates the acquisition of metastatic traits by altering the mevalonate pathway
title_fullStr Loss of dyskerin facilitates the acquisition of metastatic traits by altering the mevalonate pathway
title_full_unstemmed Loss of dyskerin facilitates the acquisition of metastatic traits by altering the mevalonate pathway
title_sort Loss of dyskerin facilitates the acquisition of metastatic traits by altering the mevalonate pathway
dc.creator.none.fl_str_mv Andrades, Evelyn
Toll Abelló, Agustín
Deza, Gustavo
Segura Tigell, Sonia
Gimeno, Ramón
Espadas, Guadalupe
Sabidó Aguadé, Eduard, 1981-
Haro, Noemí
Pozo Mendoza, Óscar J., 1975-
Bódalo-Torruella, Marta
Torres, Paloma
Pujol Vallverdú, Ramón M.
Hernández-Muñoz, Inmaculada
author Andrades, Evelyn
author_facet Andrades, Evelyn
Toll Abelló, Agustín
Deza, Gustavo
Segura Tigell, Sonia
Gimeno, Ramón
Espadas, Guadalupe
Sabidó Aguadé, Eduard, 1981-
Haro, Noemí
Pozo Mendoza, Óscar J., 1975-
Bódalo-Torruella, Marta
Torres, Paloma
Pujol Vallverdú, Ramón M.
Hernández-Muñoz, Inmaculada
author_role author
author2 Toll Abelló, Agustín
Deza, Gustavo
Segura Tigell, Sonia
Gimeno, Ramón
Espadas, Guadalupe
Sabidó Aguadé, Eduard, 1981-
Haro, Noemí
Pozo Mendoza, Óscar J., 1975-
Bódalo-Torruella, Marta
Torres, Paloma
Pujol Vallverdú, Ramón M.
Hernández-Muñoz, Inmaculada
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer
Sistema limfàtic
Metàstasi limfàtica
topic Càncer
Sistema limfàtic
Metàstasi limfàtica
description The initial dissemination of cancer cells from many primary tumors implies intravasation to lymphatic nodes or blood vessels. To investigate the mechanisms involved, we analyzed the expression of small non-coding RNAs in cutaneous squamous cell carcinoma (cSCC), a prevalent tumor that mainly spreads to lymph nodes. We report the reduced expression of small nucleolar RNAs in primary cSCCs that metastasized when compared to non-metastasizing cSCCs, and the progressive loss of DKC1 (dyskerin, which stabilizes the small nucleolar RNAs) along the metastasis. DKC1 depletion in cSCC cells triggered lipid metabolism by altering the mevalonate pathway and the acquisition of metastatic traits. Treatment of DKC1-depleted cells with simvastatin, an inhibitor of the mevalonate pathway, blocked the expression of proteins involved in the epithelial-to-mesenchymal transition. Consistently, the expression of the enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 1 was associated with pathological features of high metastatic risk in cSCC patients. Our data underpin the relevance of the mevalonate metabolism in metastatic dissemination and pave the possible incorporation of therapeutic approaches among the antineoplastic drugs used in routine patient care.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
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 http://hdl.handle.net/10230/57244
http://dx.doi.org/10.26508/lsa.202201692
url http://hdl.handle.net/10230/57244
http://dx.doi.org/10.26508/lsa.202201692
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Life Science Alliance. 2023 Apr;6(4):e20220169
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Life Science Alliance LLC
publisher.none.fl_str_mv Life Science Alliance LLC
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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