The BTB-zinc finger transcription factor abrupt acts as an epithelial oncogene in drosophila melanogaster through maintaining a progenitor-like cell state

The capacity of tumour cells to maintain continual overgrowth potential has been linked to the commandeering of normal self-renewal pathways. Using an epithelial cancer model in Drosophila melanogaster, we carried out an overexpression screen for oncogenes capable of cooperating with the loss of the...

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Autores: Turkel, Nezaket, Sahota, Virender K., Bolden, Jessica E., Goulding, Karen R., Doggett, Karen, Willoughby, Lee F., Blanco, Enrique, Martín Blanco, Enrique, Corominas, Montserrat (Corominas Guiu), Ellul, Jason, Aigaki, Toshiro, Richardson, Helena E., Brumby, Anthony M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/96207
Acceso en línea:https://hdl.handle.net/2445/96207
Access Level:acceso abierto
Palabra clave:Drosòfila melanogaster
Cèl·lules epitelials
Factors de transcripció
Tumors
Drosophila melanogaster
Epithelial cells
Transcription factors
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repository_id_str
spelling The BTB-zinc finger transcription factor abrupt acts as an epithelial oncogene in drosophila melanogaster through maintaining a progenitor-like cell stateTurkel, NezaketSahota, Virender K.Bolden, Jessica E.Goulding, Karen R.Doggett, KarenWilloughby, Lee F.Blanco, EnriqueMartín Blanco, EnriqueCorominas, Montserrat (Corominas Guiu)Ellul, JasonAigaki, ToshiroRichardson, Helena E.Brumby, Anthony M.Drosòfila melanogasterCèl·lules epitelialsFactors de transcripcióTumorsDrosophila melanogasterEpithelial cellsTranscription factorsTumorsThe capacity of tumour cells to maintain continual overgrowth potential has been linked to the commandeering of normal self-renewal pathways. Using an epithelial cancer model in Drosophila melanogaster, we carried out an overexpression screen for oncogenes capable of cooperating with the loss of the epithelial apico-basal cell polarity regulator, scribbled (scrib), and identified the cell fate regulator, Abrupt, a BTB-zinc finger protein. Abrupt overexpression alone is insufficient to transform cells, but in cooperation with scrib loss of function, Abrupt promotes the formation of massive tumours in the eye/antennal disc. The steroid hormone receptor coactivator, Taiman (a homologue of SRC3/AIB1), is known to associate with Abrupt, and Taiman overexpression also drives tumour formation in cooperation with the loss of Scrib. Expression arrays and ChIP-Seq indicates that Abrupt overexpression represses a large number of genes, including steroid hormone-response genes and multiple cell fate regulators, thereby maintaining cells within an epithelial progenitor-like state. The progenitor-like state is characterised by the failure to express the conserved Eyes absent/Dachshund regulatory complex in the eye disc, and in the antennal disc by the failure to express cell fate regulators that define the temporal elaboration of the appendage along the proximo-distal axis downstream of Distalless. Loss of scrib promotes cooperation with Abrupt through impaired Hippo signalling, which is required and sufficient for cooperative overgrowth with Abrupt, and JNK (Jun kinase) signalling, which is required for tumour cell migration/invasion but not overgrowth. These results thus identify a novel cooperating oncogene, identify mammalian family members of which are also known oncogenes, and demonstrate that epithelial tumours in Drosophila can be characterised by the maintenance of a progenitor-like state.Public Library of Science (PLoS)2016201620132016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion24 p.application/pdfhttps://hdl.handle.net/2445/96207Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: http://dx.doi.org/10.1371/journal.pgen.1003627PLoS Genetics, 2013, vol. 9, num. 7, p. e1003627-e1003627http://dx.doi.org/10.1371/journal.pgen.1003627cc-by (c) Turkel, Nezaket et al., 2013http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/962072026-05-29T05:05:01Z
dc.title.none.fl_str_mv The BTB-zinc finger transcription factor abrupt acts as an epithelial oncogene in drosophila melanogaster through maintaining a progenitor-like cell state
title The BTB-zinc finger transcription factor abrupt acts as an epithelial oncogene in drosophila melanogaster through maintaining a progenitor-like cell state
spellingShingle The BTB-zinc finger transcription factor abrupt acts as an epithelial oncogene in drosophila melanogaster through maintaining a progenitor-like cell state
Turkel, Nezaket
Drosòfila melanogaster
Cèl·lules epitelials
Factors de transcripció
Tumors
Drosophila melanogaster
Epithelial cells
Transcription factors
Tumors
title_short The BTB-zinc finger transcription factor abrupt acts as an epithelial oncogene in drosophila melanogaster through maintaining a progenitor-like cell state
title_full The BTB-zinc finger transcription factor abrupt acts as an epithelial oncogene in drosophila melanogaster through maintaining a progenitor-like cell state
title_fullStr The BTB-zinc finger transcription factor abrupt acts as an epithelial oncogene in drosophila melanogaster through maintaining a progenitor-like cell state
title_full_unstemmed The BTB-zinc finger transcription factor abrupt acts as an epithelial oncogene in drosophila melanogaster through maintaining a progenitor-like cell state
title_sort The BTB-zinc finger transcription factor abrupt acts as an epithelial oncogene in drosophila melanogaster through maintaining a progenitor-like cell state
dc.creator.none.fl_str_mv Turkel, Nezaket
Sahota, Virender K.
Bolden, Jessica E.
Goulding, Karen R.
Doggett, Karen
Willoughby, Lee F.
Blanco, Enrique
Martín Blanco, Enrique
Corominas, Montserrat (Corominas Guiu)
Ellul, Jason
Aigaki, Toshiro
Richardson, Helena E.
Brumby, Anthony M.
author Turkel, Nezaket
author_facet Turkel, Nezaket
Sahota, Virender K.
Bolden, Jessica E.
Goulding, Karen R.
Doggett, Karen
Willoughby, Lee F.
Blanco, Enrique
Martín Blanco, Enrique
Corominas, Montserrat (Corominas Guiu)
Ellul, Jason
Aigaki, Toshiro
Richardson, Helena E.
Brumby, Anthony M.
author_role author
author2 Sahota, Virender K.
Bolden, Jessica E.
Goulding, Karen R.
Doggett, Karen
Willoughby, Lee F.
Blanco, Enrique
Martín Blanco, Enrique
Corominas, Montserrat (Corominas Guiu)
Ellul, Jason
Aigaki, Toshiro
Richardson, Helena E.
Brumby, Anthony M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Drosòfila melanogaster
Cèl·lules epitelials
Factors de transcripció
Tumors
Drosophila melanogaster
Epithelial cells
Transcription factors
Tumors
topic Drosòfila melanogaster
Cèl·lules epitelials
Factors de transcripció
Tumors
Drosophila melanogaster
Epithelial cells
Transcription factors
Tumors
description The capacity of tumour cells to maintain continual overgrowth potential has been linked to the commandeering of normal self-renewal pathways. Using an epithelial cancer model in Drosophila melanogaster, we carried out an overexpression screen for oncogenes capable of cooperating with the loss of the epithelial apico-basal cell polarity regulator, scribbled (scrib), and identified the cell fate regulator, Abrupt, a BTB-zinc finger protein. Abrupt overexpression alone is insufficient to transform cells, but in cooperation with scrib loss of function, Abrupt promotes the formation of massive tumours in the eye/antennal disc. The steroid hormone receptor coactivator, Taiman (a homologue of SRC3/AIB1), is known to associate with Abrupt, and Taiman overexpression also drives tumour formation in cooperation with the loss of Scrib. Expression arrays and ChIP-Seq indicates that Abrupt overexpression represses a large number of genes, including steroid hormone-response genes and multiple cell fate regulators, thereby maintaining cells within an epithelial progenitor-like state. The progenitor-like state is characterised by the failure to express the conserved Eyes absent/Dachshund regulatory complex in the eye disc, and in the antennal disc by the failure to express cell fate regulators that define the temporal elaboration of the appendage along the proximo-distal axis downstream of Distalless. Loss of scrib promotes cooperation with Abrupt through impaired Hippo signalling, which is required and sufficient for cooperative overgrowth with Abrupt, and JNK (Jun kinase) signalling, which is required for tumour cell migration/invasion but not overgrowth. These results thus identify a novel cooperating oncogene, identify mammalian family members of which are also known oncogenes, and demonstrate that epithelial tumours in Drosophila can be characterised by the maintenance of a progenitor-like state.
publishDate 2013
dc.date.none.fl_str_mv 2013
2016
2016
2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/96207
url https://hdl.handle.net/2445/96207
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pgen.1003627
PLoS Genetics, 2013, vol. 9, num. 7, p. e1003627-e1003627
http://dx.doi.org/10.1371/journal.pgen.1003627
dc.rights.none.fl_str_mv cc-by (c) Turkel, Nezaket et al., 2013
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Turkel, Nezaket et al., 2013
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 24 p.
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Genètica, Microbiologia i Estadística)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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