Please use this identifier to cite or link to this item:
http://hdl.handle.net/10397/60977
DC Field | Value | Language |
---|---|---|
dc.contributor | Department of Applied Biology and Chemical Technology | - |
dc.creator | Wu, J | - |
dc.creator | Keng, VW | - |
dc.creator | Patmore, DM | - |
dc.creator | Kendall, JJ | - |
dc.creator | Patel, AV | - |
dc.creator | Jousma, E | - |
dc.creator | Jessen, WJ | - |
dc.creator | Choi, K | - |
dc.creator | Tschida, BR | - |
dc.creator | Silverstein, KAT | - |
dc.creator | Fan, D | - |
dc.creator | Schwartz, EB | - |
dc.creator | Fuchs, JR | - |
dc.creator | Zou, Y | - |
dc.creator | Kim, MO | - |
dc.creator | Dombi, E | - |
dc.creator | Levy, DE | - |
dc.creator | Huang, G | - |
dc.creator | Cancelas, JA | - |
dc.creator | Stemmer-Rachamimov, AO | - |
dc.creator | Spinner, RJ | - |
dc.creator | Largaespada, DA | - |
dc.creator | Ratner, N | - |
dc.date.accessioned | 2016-12-19T08:54:14Z | - |
dc.date.available | 2016-12-19T08:54:14Z | - |
dc.identifier.issn | 2211-1247 | en_US |
dc.identifier.uri | http://hdl.handle.net/10397/60977 | - |
dc.language.iso | en | en_US |
dc.publisher | Cell Press | en_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.rights | The 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.2016.01.074 | en_US |
dc.title | Insertional mutagenesis identifies a STAT3/Arid1b/β-catenin pathway driving neurofibroma initiation | en_US |
dc.type | Journal/Magazine Article | en_US |
dc.identifier.spage | 1979 | en_US |
dc.identifier.epage | 1990 | en_US |
dc.identifier.volume | 14 | en_US |
dc.identifier.issue | 8 | en_US |
dc.identifier.doi | 10.1016/j.celrep.2016.01.074 | en_US |
dcterms.abstract | To 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.accessRights | open access | en_US |
dcterms.bibliographicCitation | Cell reports, 2016, v. 14, no. 8, p. 1979-1990 | - |
dcterms.isPartOf | Cell reports | - |
dcterms.issued | 2016 | - |
dc.identifier.isi | WOS:000371217700017 | - |
dc.identifier.scopus | 2-s2.0-84959181076 | - |
dc.identifier.pmid | 26904939 | - |
dc.identifier.rosgroupid | 2015000648 | - |
dc.description.ros | 2015-2016 > Academic research: refereed > Publication in refereed journal | en_US |
dc.description.validate | 201901_a bcma | en_US |
dc.description.oa | Version of Record | en_US |
dc.identifier.FolderNumber | OA_IR/PIRA | en_US |
dc.description.pubStatus | Published | en_US |
Appears in Collections: | Journal/Magazine Article |
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File | Description | Size | Format | |
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Wu_Insertional_mutagenesis_identifies.pdf | 4.09 MB | Adobe PDF | View/Open |
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