2009 |
Rodilla, Verónica, Villanueva, Alberto, Obrador-Hevia, Antonia, Robert-Moreno, Alex, Fernández-Majada, Vanessa, Grilli, Andrea, López-Bigas, Nuria, Bellora, Nicolás, Albà, M Mar, Torres, Ferran, Duñach, Mireia, Sanjuan, Xavier, Gonzalez, Sara, Gridley, Thomas, Capella, Gabriel, Bigas, Anna, Espinosa, Lluís Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancer. (Article) Proceedings of the National Academy of Sciences of the United States of America, 106 (15), pp. 6315–20, 2009, ISSN: 1091-6490. (Abstract | Links | BibTeX | Tags: 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) @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} } 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. |
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Amino Acid Animals Computational Biology Databases de novo gene DNA Evolution Genetic Genome Humans lncRNA Mice Molecular Molecular Sequence Data Nucleic Acid Proteins Proteins: chemistry Proteins: genetics Repetitive Sequences ribosome profiling RNA-Seq Sequence Analysis Sequence Homology transcriptomics yeast
2009 |
Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancer. (Article) Proceedings of the National Academy of Sciences of the United States of America, 106 (15), pp. 6315–20, 2009, ISSN: 1091-6490. |