Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

NOTCH pathway inactivation promotes bladder cancer progression

Abstract : NOTCH signaling suppresses tumor growth and proliferation in several types of stratified epithelia. Here, we show that missense mutations in NOTCH1 and NOTCH2 found in human bladder cancers result in loss of function. In murine models, genetic ablation of the NOTCH pathway accelerated bladder tumorigenesis and promoted the formation of squamous cell carcinomas, with areas of mesenchymal features. Using bladder cancer cells, we determined that the NOTCH pathway stabilizes the epithelial phenotype through its effector HES1 and, consequently, loss of NOTCH activity favors the process of epithelial-mesenchymal transition. Evaluation of human bladder cancer samples revealed that tumors with low levels of HES1 present mesenchymal features and are more aggressive. Together, our results indicate that NOTCH serves as a tumor suppressor in the bladder and that loss of this pathway promotes mesenchymal and invasive features.
Liste complète des métadonnées

Littérature citée [52 références]  Voir  Masquer  Télécharger
Contributeur : Mélanie Karli <>
Soumis le : mardi 3 septembre 2019 - 16:11:50
Dernière modification le : mercredi 4 septembre 2019 - 15:46:51
Document(s) archivé(s) le : mercredi 5 février 2020 - 21:55:26


Fichiers éditeurs autorisés sur une archive ouverte




Antonio Maraver, Pablo Fernandez-Marcos, Timothy Cash, Marinela Mendez-Pertuz, Marta Dueñas, et al.. NOTCH pathway inactivation promotes bladder cancer progression. Journal of Clinical Investigation, American Society for Clinical Investigation, 2015, 125 (2), pp.824-830. ⟨10.1172/JCI78185⟩. ⟨hal-02277493⟩



Consultations de la notice


Téléchargements de fichiers