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http://hdl.handle.net/2445/187105
Title: | P53 wild-type colorectal cancer cells that express a fetal gene signature are associated with metastasis and poor prognosis |
Author: | Solé, Laura Lobo Jarne, Teresa Álvarez Villanueva, Daniel Alonso Marañón, Josune Guillén, Yolanda Guix, Marta Sangrador Escrig, Irene Rozalén, Catalina Vert, Anna Barbachano, Antonio Lop, Joan Salido, Marta Bellosillo, Beatriz García Romero, Raquel Garrido, Marta González, Jessica Martínez Iniesta, María López Arribillaga, Erika Salazar, Ramón Montagut, Clara Torres, Ferrán Iglesias, Mar Celià Terrassa, Toni Muñoz, Alberto Villanueva, Alberto Bigas, Anna Espinosa, Lluís |
Keywords: | Càncer colorectal Genètica humana Colorectal cancer Human genetics |
Issue Date: | 23-May-2022 |
Publisher: | Springer |
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. The failure of chemotherapy in colorectal cancer is currently unclear. Here, the authors show that upon sub-lethal dose of chemotherapy wild-type p53 colorectal cancers acquire a quiescence-like phenotype and a YAP-dependent fetal-like intestinal stem cell state associated with a higher metastatic activity and poor prognosis in patients. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41467-022-30382-9 |
It is part of: | Nature Communications, 2022, vol. 13, num. 1 |
URI: | http://hdl.handle.net/2445/187105 |
Related resource: | https://doi.org/10.1038/s41467-022-30382-9 |
ISSN: | 2041-1723 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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