p53 wild-type colorectal cancer cells that express a fetal gene signature are associated with metastasis and poor prognosis

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• dc.contributor.author Solé, Laura
• dc.contributor.author Lobo-Jarne, Teresa
• dc.contributor.author Álvarez-Villanueva, Daniel
• dc.contributor.author Alonso-Marañón, Josune
• dc.contributor.author Guillén, Yolanda
• dc.contributor.author Guix Arnau, Marta, 1974-
• dc.contributor.author Sangrador, Irene
• dc.contributor.author Rozalén, Catalina
• dc.contributor.author Vert, Anna
• dc.contributor.author Lop Gros, Joan
• dc.contributor.author Salido Galeote, Marta
• dc.contributor.author Bellosillo Paricio, Beatriz
• dc.contributor.author García-Romero, Raquel
• dc.contributor.author Garrido, Marta
• dc.contributor.author González, Jessica
• dc.contributor.author López Arribillaga, Erika, 1986-
• dc.contributor.author Iglesias Coma, Mar
• dc.contributor.author Celià-Terrassa, Toni
• dc.contributor.author Bigas Salvans, Anna
• dc.contributor.author Espinosa Blay, Lluís
• dc.date.accessioned 2022-11-25T07:42:24Z
• dc.date.available 2022-11-25T07:42:24Z
• dc.date.issued 2022
• dc.description.abstract Current therapy against colorectal cancer (CRC) is based on DNA-damaging agents that remain ineffective in a proportion of patients. Whether and how non-curative DNA damage-based treatment affects tumor cell behavior and patient outcome is primarily unstudied. Using CRC patient-derived organoids (PDO)s, we show that sublethal doses of chemotherapy (CT) does not select previously resistant tumor populations but induces a quiescent state specifically to TP53 wildtype (WT) cancer cells, which is linked to the acquisition of a YAP1-dependent fetal phenotype. Cells displaying this phenotype exhibit high tumor-initiating and metastatic activity. Nuclear YAP1 and fetal traits are present in a proportion of tumors at diagnosis and predict poor prognosis in patients carrying TP53 WT CRC tumors. We provide data indicating the higher efficacy of CT together with YAP1 inhibitors for eradication of therapy resistant TP53 WT cancer cells. Together these results identify fetal conversion as a useful biomarker for patient prognosis and therapy prescription.
• dc.format.mimetype application/pdf
• dc.identifier.citation Solé L, Lobo-Jarne T, Álvarez-Villanueva D, Alonso-Marañón J, Guillén Y, Guix M, et al. p53 wild-type colorectal cancer cells that express a fetal gene signature are associated with metastasis and poor prognosis. Nat Commun. 2022 May 23; 13(1): 2866. DOI: 10.1038/s41467-022-30382-9
• dc.identifier.doi http://dx.doi.org/10.1038/s41467-022-30382-9
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/55004
• dc.language.iso eng
• dc.publisher Nature Research
• dc.rights Copyright © Solé L, Lobo-Jarne T, Álvarez-Villanueva D, Alonso-Marañón J, Guillén Y, Guix M, et al. 2022. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://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 Còlon--Càncer
• dc.subject.other Metàstasi
• dc.subject.other Còlon--Càncer--Tractament
• dc.subject.other Marcadors bioquímics
• dc.title p53 wild-type colorectal cancer cells that express a fetal gene signature are associated with metastasis and poor prognosis
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion