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Manic fringe deficiency imposes jagged1 addiction to intestinal tumor cells

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dc.contributor.author López Arribillaga, Erika
dc.contributor.author Rodilla, Verónica
dc.contributor.author Colomer Montañá, Carlota
dc.contributor.author Vert, Anna
dc.contributor.author Shelton, Amy
dc.contributor.author Cheng, Jason H.
dc.contributor.author Yan, Bing
dc.contributor.author González Pérez, Abel
dc.contributor.author Junttila, Melissa R.
dc.contributor.author Iglesias Coma, Mar
dc.contributor.author Torres, Ferran
dc.contributor.author Albanell Mestres, Joan
dc.contributor.author Villanueva, Alberto
dc.contributor.author Bigas Salvans, Anna
dc.contributor.author Siebel, Christian W.
dc.contributor.author Espinosa Blay, Lluís
dc.date.accessioned 2019-06-14T07:39:32Z
dc.date.available 2019-06-14T07:39:32Z
dc.date.issued 2018
dc.identifier.citation López-Arribillaga E, Rodilla V, Colomer C, Vert A, Shelton A, Cheng JH. Et al. Manic fringe deficiency imposes jagged1 addiction to intestinal tumor cells. Nat Commun. 2018 Jul 31;9(1):2992. DOI: 10.1038/s41467-018-05385-0
dc.identifier.issn 2041-1723
dc.identifier.uri http://hdl.handle.net/10230/41754
dc.description.abstract Delta ligands regulate Notch signaling in normal intestinal stem cells, while Jagged1 activates Notch in intestinal adenomas carrying active β-catenin. We used the ApcMin/+ mouse model, tumor spheroid cultures, and patient-derived orthoxenografts to address this divergent ligand-dependent Notch function and its implication in disease. We found that intestinal-specific Jag1 deletion or antibody targeting Jag1 prevents tumor initiation in mice. Addiction to Jag1 is concomitant with the absence of Manic Fringe (MFNG) in adenoma cells, and its ectopic expression reverts Jag1 dependence. In 239 human colorectal cancer patient samples, MFNG imposes a negative correlation between Jag1 and Notch, being high Jag1 in the absence of MFNG predictive of poor prognosis. Jag1 antibody treatment reduces patient-derived tumor orthoxenograft growth without affecting normal intestinal mucosa. Our data provide an explanation to Jag1 dependence in cancer, and reveal that Jag1-Notch1 interference provides therapeutic benefit in a subset of colorectal cancer and FAP syndrome patients.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Research
dc.rights copyright © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.other Intestins -- Càncer
dc.subject.other Intestins -- Malalties
dc.title Manic fringe deficiency imposes jagged1 addiction to intestinal tumor cells
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/s41467-018-05385-0
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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