Please use this identifier to cite or link to this item: 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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