Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/60977
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dc.contributorDepartment of Applied Biology and Chemical Technology-
dc.creatorWu, J-
dc.creatorKeng, VW-
dc.creatorPatmore, DM-
dc.creatorKendall, JJ-
dc.creatorPatel, AV-
dc.creatorJousma, E-
dc.creatorJessen, WJ-
dc.creatorChoi, K-
dc.creatorTschida, BR-
dc.creatorSilverstein, KAT-
dc.creatorFan, D-
dc.creatorSchwartz, EB-
dc.creatorFuchs, JR-
dc.creatorZou, Y-
dc.creatorKim, MO-
dc.creatorDombi, E-
dc.creatorLevy, DE-
dc.creatorHuang, G-
dc.creatorCancelas, JA-
dc.creatorStemmer-Rachamimov, AO-
dc.creatorSpinner, RJ-
dc.creatorLargaespada, DA-
dc.creatorRatner, N-
dc.date.accessioned2016-12-19T08:54:14Z-
dc.date.available2016-12-19T08:54:14Z-
dc.identifier.issn2211-1247en_US
dc.identifier.urihttp://hdl.handle.net/10397/60977-
dc.language.isoenen_US
dc.publisherCell Pressen_US
dc.rights© 2016 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.rightsThe following publication Wu, J., Keng, V. W., Patmore, D. M., Kendall, J. J., Patel, A. V., Jousma, E., ... & Fan, D. (2016). Insertional mutagenesis identifies a STAT3/Arid1b/β-catenin pathway driving neurofibroma initiation. Cell reports, 14(8), 1979-1990, is available at https://doi.org/10.1016/j.celrep.2016.01.074en_US
dc.titleInsertional mutagenesis identifies a STAT3/Arid1b/β-catenin pathway driving neurofibroma initiationen_US
dc.typeJournal/Magazine Articleen_US
dc.identifier.spage1979en_US
dc.identifier.epage1990en_US
dc.identifier.volume14en_US
dc.identifier.issue8en_US
dc.identifier.doi10.1016/j.celrep.2016.01.074en_US
dcterms.abstractTo identify genes and signaling pathways that initiate Neurofibromatosis type 1 (NF1) neurofibromas, we used unbiased insertional mutagenesis screening, mouse models, and molecular analyses. We mapped an Nf1-Stat3-Arid1b/β-catenin pathway that becomes active in the context of Nf1 loss. Genetic deletion of Stat3 in Schwann cell progenitors (SCPs) and Schwann cells (SCs) prevents neurofibroma formation, decreasing SCP self-renewal and β-catenin activity. β-catenin expression rescues effects of Stat3 loss in SCPs. Importantly, P-STAT3 and β-catenin expression correlate in human neurofibromas. Mechanistically, P-Stat3 represses Gsk3β and the SWI/SNF gene Arid1b to increase β-catenin. Knockdown of Arid1b or Gsk3β in Stat3fl/fl;Nf1fl/fl;DhhCre SCPs rescues neurofibroma formation after in vivo transplantation. Stat3 represses Arid1b through histone modification in a Brg1-dependent manner, indicating that epigenetic modification plays a role in early tumorigenesis. Our data map a neural tumorigenesis pathway and support testing JAK/STAT and Wnt/β-catenin pathway inhibitors in neurofibroma therapeutic trials.-
dcterms.accessRightsopen accessen_US
dcterms.bibliographicCitationCell reports, 2016, v. 14, no. 8, p. 1979-1990-
dcterms.isPartOfCell reports-
dcterms.issued2016-
dc.identifier.isiWOS:000371217700017-
dc.identifier.scopus2-s2.0-84959181076-
dc.identifier.pmid26904939-
dc.identifier.rosgroupid2015000648-
dc.description.ros2015-2016 > Academic research: refereed > Publication in refereed journalen_US
dc.description.validate201901_a bcmaen_US
dc.description.oaVersion of Recorden_US
dc.identifier.FolderNumberOA_IR/PIRAen_US
dc.description.pubStatusPublisheden_US
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