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NOTCH pathway inactivation promotes bladder cancer progression
- Source :
- Journal of Clinical Investigation, Journal of Clinical Investigation, American Society for Clinical Investigation, 2015, 125 (2), pp.824-830. ⟨10.1172/JCI78185⟩
- Publication Year :
- 2015
- Publisher :
- HAL CCSD, 2015.
-
Abstract
- International audience; 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.
- Subjects :
- Pathology
medicine.medical_specialty
Bladder cancer
Mesenchymal stem cell
Notch signaling pathway
Cancer
[SDV.CAN]Life Sciences [q-bio]/Cancer
General Medicine
Biology
medicine.disease
medicine.disease_cause
3. Good health
[SDV.CAN] Life Sciences [q-bio]/Cancer
Notch proteins
Cancer research
medicine
Epithelial–mesenchymal transition
HES1
Carcinogenesis
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Investigation, Journal of Clinical Investigation, American Society for Clinical Investigation, 2015, 125 (2), pp.824-830. ⟨10.1172/JCI78185⟩
- Accession number :
- edsair.doi.dedup.....d61f78c32298ea4579522f1fc874cbe5