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Usage Information

NOTCH pathway inactivation promotes bladder cancer progression
Antonio Maraver, … , Francisco X. Real, Manuel Serrano
Antonio Maraver, … , Francisco X. Real, Manuel Serrano
Published January 9, 2015
Citation Information: J Clin Invest. 2015;125(2):824-830. https://doi.org/10.1172/JCI78185.
View: Text | PDF
Research Article

NOTCH pathway inactivation promotes bladder cancer progression

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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.

Authors

Antonio Maraver, Pablo J. Fernandez-Marcos, Timothy P. Cash, Marinela Mendez-Pertuz, Marta Dueñas, Paolo Maietta, Paola Martinelli, Maribel Muñoz-Martin, Mónica Martínez-Fernández, Marta Cañamero, Giovanna Roncador, Jorge L. Martinez-Torrecuadrada, Dimitrios Grivas, Jose Luis de la Pompa, Alfonso Valencia, Jesús M. Paramio, Francisco X. Real, Manuel Serrano

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Usage data is cumulative from July 2024 through July 2025.

Usage JCI PMC
Text version 627 112
PDF 86 45
Figure 319 6
Supplemental data 44 7
Citation downloads 81 0
Totals 1,157 170
Total Views 1,327
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Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.

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