Publication List

@article{Rodilla2009,
title = {Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancer.},
author = {Rodilla, Verónica and Villanueva, Alberto and Obrador-Hevia, Antonia and Robert-Moreno, Alex and Fernández-Majada, Vanessa and Grilli, Andrea and López-Bigas, Nuria and Bellora, Nicolás and Albà, M Mar and Torres, Ferran and Duñach, Mireia and Sanjuan, Xavier and Gonzalez, Sara and Gridley, Thomas and Capella, Gabriel and Bigas, Anna and Espinosa, Lluís},
url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2669348&tool=pmcentrez&rendertype=abstract},
issn = {1091-6490},
year = {2009},
date = {2009-01-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {106},
number = {15},
pages = {6315--20},
abstract = {Notch has been linked to beta-catenin-dependent tumorigenesis; however, the mechanisms leading to Notch activation and the contribution of the Notch pathway to colorectal cancer is not yet understood. By microarray analysis, we have identified a group of genes downstream of Wnt/beta-catenin (down-regulated when blocking Wnt/beta-catenin) that are directly regulated by Notch (repressed by gamma-secretase inhibitors and up-regulated by active Notch1 in the absence of beta-catenin signaling). We demonstrate that Notch is downstream of Wnt in colorectal cancer cells through beta-catenin-mediated transcriptional activation of the Notch-ligand Jagged1. Consistently, expression of activated Notch1 partially reverts the effects of blocking Wnt/beta-catenin pathway in tumors implanted s.c. in nude mice. Crossing APC(Min/+) with Jagged1(+/Delta) mice is sufficient to significantly reduce the size of the polyps arising in the APC mutant background indicating that Notch is an essential modulator of tumorigenesis induced by nuclear beta-catenin. We show that this mechanism is operating in human tumors from Familial Adenomatous Polyposis patients. We conclude that Notch activation, accomplished by beta-catenin-mediated up-regulation of Jagged1, is required for tumorigenesis in the intestine. The Notch-specific genetic signature is sufficient to block differentiation and promote vasculogenesis in tumors whereas proliferation depends on both pathways.},
keywords = {Alleles, Animals, beta Catenin, beta Catenin: metabolism, Calcium-Binding Proteins, Calcium-Binding Proteins: genetics, Calcium-Binding Proteins: metabolism, Cell Line, Cell Nucleus, Cell Nucleus: metabolism, Colorectal Neoplasms, Colorectal Neoplasms: blood supply, Colorectal Neoplasms: genetics, Colorectal Neoplasms: metabolism, Colorectal Neoplasms: pathology, Gene Expression Profiling, Gene Expression Regulation, Genetic, Genetic: genetics, Humans, Intercellular Signaling Peptides and Proteins, Intercellular Signaling Peptides and Proteins: gen, Intercellular Signaling Peptides and Proteins: met, Membrane Proteins, Membrane Proteins: genetics, Membrane Proteins: metabolism, Mice, Neoplastic, Notch, Notch: metabolism, Receptors, Signal Transduction, TCF Transcription Factors, TCF Transcription Factors: metabolism, Transcription, Transgenic, Wnt Proteins, Wnt Proteins: metabolism}
}