Loss of dyskerin facilitates the acquisition of metastatic traits by altering the mevalonate pathway
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- dc.contributor.author Andrades, Evelyn
- dc.contributor.author Toll Abelló, Agustín
- dc.contributor.author Deza, Gustavo
- dc.contributor.author Segura Tigell, Sonia
- dc.contributor.author Gimeno, Ramón
- dc.contributor.author Espadas, Guadalupe
- dc.contributor.author Sabidó, Eduard
- dc.contributor.author Haro, Noemí
- dc.contributor.author Pozo, Óscar J.
- dc.contributor.author Bódalo-Torruella, Marta
- dc.contributor.author Torres, Paloma
- dc.contributor.author Pujol Vallverdú, Ramon Maria
- dc.contributor.author Hernández-Muñoz, Inmaculada
- dc.date.accessioned 2023-06-20T06:20:14Z
- dc.date.available 2023-06-20T06:20:14Z
- dc.date.issued 2023
- dc.description.abstract 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.
- dc.format.mimetype application/pdf
- dc.identifier.citation Andrades E, Toll A, Deza G, Segura S, Gimeno R, Espadas G, et al. Loss of dyskerin facilitates the acquisition of metastatic traits by altering the mevalonate pathway. Life Sci Alliance. 2023 Apr;6(4):e202201692. DOI: 10.26508/lsa.202201692
- dc.identifier.doi http://dx.doi.org/10.26508/lsa.202201692
- dc.identifier.issn 2575-1077
- dc.identifier.uri http://hdl.handle.net/10230/57244
- dc.language.iso eng
- dc.publisher Life Science Alliance LLC
- dc.relation.ispartof Life Science Alliance. 2023 Apr;6(4):e20220169
- dc.rights © 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/.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.other Càncer
- dc.subject.other Sistema limfàtic
- dc.subject.other Metàstasi limfàtica
- dc.title Loss of dyskerin facilitates the acquisition of metastatic traits by altering the mevalonate pathway
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion