Cross-talk between YAP and RAR-RXR Drives ...
Type de document :
Compte-rendu et recension critique d'ouvrage
PMID :
Titre :
Cross-talk between YAP and RAR-RXR Drives Expression of Stemness Genes to Promote 5-FU Resistance and Self-Renewal in Colorectal Cancer Cells
Auteur(s) :
Bauzone, Marjolaine [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Souidi, Mouloud [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Dessein, Anne-Frédérique [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Wisztorski (Admin), Maxence [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Vincent, Audrey [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Gimeno, jean-pascal [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Monté, Didier [Auteur]
Biologie Structurale Intégrative [ERL 9002 - BSI ]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
VAN SEUNINGEN, ISABELLE [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Gespach, Christian [Auteur]
Centre de Recherche Saint-Antoine [CRSA]
Huet, Guillemette [Auteur correspondant]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Souidi, Mouloud [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Dessein, Anne-Frédérique [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Wisztorski (Admin), Maxence [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Vincent, Audrey [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Gimeno, jean-pascal [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 [PRISM]
Monté, Didier [Auteur]
Biologie Structurale Intégrative [ERL 9002 - BSI ]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
VAN SEUNINGEN, ISABELLE [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Gespach, Christian [Auteur]
Centre de Recherche Saint-Antoine [CRSA]
Huet, Guillemette [Auteur correspondant]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Titre de la revue :
Molecular Cancer Research
Pagination :
612-622
Éditeur :
American Association for Cancer Research
Date de publication :
2021-04-02
ISSN :
1541-7786
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
The mechanisms whereby the Hippo pathway effector YAP regulates cancer cell stemness, plasticity, and chemoresistance are not fully understood. We previously showed that in 5-fluorouracil (5-FU)–resistant colorectal cancer ...
Lire la suite >The mechanisms whereby the Hippo pathway effector YAP regulates cancer cell stemness, plasticity, and chemoresistance are not fully understood. We previously showed that in 5-fluorouracil (5-FU)–resistant colorectal cancer cells, the transcriptional coactivator YAP is differentially regulated at critical transitions connected with reversible quiescence/dormancy to promote metastasis. Here, we found that experimental YAP activation in 5-FU–sensitive and 5-FU–resistant HT29 colorectal cancer cells enhanced nuclear YAP localization and the transcript levels of the retinoic acid (RA) receptors RARα/γ and RAR target genes CYP26A1, ALDH1A3, and LGR5 through RA Response Elements (RARE). In these two cell models, constitutive YAP activation reinforced the expression of the stemness biomarkers and regulators ALDH1A3, LGR5, and OCT4. Conversely, YAP silencing, RAR/RXR inhibition by the pan-RAR antagonist BMS493, and vitamin A depletion downregulated stemness traits and self-renewal. Regarding the mechanisms engaged, proximity-dependent labeling, nuclear YAP pulldown coupled with mass spectrometry, and chromatin immunoprecipitation (ChIP)/re-ChIP experiments revealed: (i) the nuclear colocalization/interaction of YAP with RARγ and RXRs; and (ii) combined genomic co-occupancy of YAP, RARα/γ, and RXRα interactomes at proximal RAREs of LGR5 and ALDH1A3 promoters. Moreover, activation of the YAP/RAR-RXR cross-talk in colorectal cancer cells promoted RAR self-activation loops via vitamin A metabolism, RA, and active RAR ligands generated by ALDH1A3. Together, our data identify YAP as a bona fide RAR-RXR transcriptional coactivator that acts through RARE-activated stemness genes.Lire moins >
Lire la suite >The mechanisms whereby the Hippo pathway effector YAP regulates cancer cell stemness, plasticity, and chemoresistance are not fully understood. We previously showed that in 5-fluorouracil (5-FU)–resistant colorectal cancer cells, the transcriptional coactivator YAP is differentially regulated at critical transitions connected with reversible quiescence/dormancy to promote metastasis. Here, we found that experimental YAP activation in 5-FU–sensitive and 5-FU–resistant HT29 colorectal cancer cells enhanced nuclear YAP localization and the transcript levels of the retinoic acid (RA) receptors RARα/γ and RAR target genes CYP26A1, ALDH1A3, and LGR5 through RA Response Elements (RARE). In these two cell models, constitutive YAP activation reinforced the expression of the stemness biomarkers and regulators ALDH1A3, LGR5, and OCT4. Conversely, YAP silencing, RAR/RXR inhibition by the pan-RAR antagonist BMS493, and vitamin A depletion downregulated stemness traits and self-renewal. Regarding the mechanisms engaged, proximity-dependent labeling, nuclear YAP pulldown coupled with mass spectrometry, and chromatin immunoprecipitation (ChIP)/re-ChIP experiments revealed: (i) the nuclear colocalization/interaction of YAP with RARγ and RXRs; and (ii) combined genomic co-occupancy of YAP, RARα/γ, and RXRα interactomes at proximal RAREs of LGR5 and ALDH1A3 promoters. Moreover, activation of the YAP/RAR-RXR cross-talk in colorectal cancer cells promoted RAR self-activation loops via vitamin A metabolism, RA, and active RAR ligands generated by ALDH1A3. Together, our data identify YAP as a bona fide RAR-RXR transcriptional coactivator that acts through RARE-activated stemness genes.Lire moins >
Langue :
Anglais
Vulgarisation :
Non
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