Mostrar el registro sencillo del ítem

dc.contributor.author
Spender, Lindsay C.
dc.contributor.author
Ferguson, John
dc.contributor.author
Liu, Sijia
dc.contributor.author
Cui, Chao
dc.contributor.author
Girotti, Maria Romina
dc.contributor.author
Sibbet, Gary
dc.contributor.author
Higgs, Ellen
dc.contributor.author
Shuttleworth, Morven K.
dc.contributor.author
Hamilton, Tom
dc.contributor.author
Lorigan, Paul
dc.contributor.author
Weller, Michael
dc.contributor.author
Vincent, David F.
dc.contributor.author
Sansom, Owen J.
dc.contributor.author
Frame, Margaret
dc.contributor.author
Dijke, Peter ten
dc.contributor.author
Marais, Richard
dc.contributor.author
Inman, Gareth J.
dc.date.available
2017-09-14T21:08:33Z
dc.date.issued
2016-11-09
dc.identifier.citation
Spender, Lindsay C.; Ferguson, John; Liu, Sijia; Cui, Chao; Girotti, Maria Romina; et al.; Mutational activation of BRAF confers sensitivity to transforming growth factor beta inhibitors in human cancer cells; Impact journals; Oncotarget; 7; 50; 9-11-2016; 81995-82012
dc.identifier.issn
1949-2553
dc.identifier.uri
http://hdl.handle.net/11336/24320
dc.description.abstract
Recent data implicate elevated transforming growth factor-β (TGFβ) signalling in BRAF inhibitor drug-resistance mechanisms, but the potential for targeting TGFβ signalling in cases of advanced melanoma has not been investigated. We show that mutant BRAFV600E confers an intrinsic dependence on TGFβ/TGFβ receptor 1 (TGFBR1) signalling for clonogenicity of murine melanocytes. Pharmacological inhibition of the TGFBR1 blocked the clonogenicity of human mutant BRAF melanoma cells through SMAD4-independent inhibition of mitosis, and also inhibited metastasis in xenografted zebrafish. When investigating the therapeutic potential of combining inhibitors of mutant BRAF and TGFBR1, we noted that unexpectedly, low-dose PLX-4720 (a vemurafenib analogue) promoted proliferation of drug-naïve melanoma cells. Pharmacological or pharmacogenetic inhibition of TGFBR1 blocked growth promotion and phosphorylation of SRC, which is frequently associated with vemurafenib-resistance mechanisms. Importantly, vemurafenib-resistant patient derived cells retained sensitivity to TGFBR1 inhibition, suggesting that TGFBR1 could be targeted therapeutically to combat the development of vemurafenib drug-resistance.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Impact journals
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
Melanoma
dc.subject
Resistance
dc.subject
Tgfb
dc.subject
Braf
dc.subject
Vemurafenib
dc.subject
Plx 4720
dc.subject
Tgf Beta
dc.subject.classification
Bioquímica y Biología Molecular
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Mutational activation of BRAF confers sensitivity to transforming growth factor beta inhibitors in human cancer cells
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-09-06T19:36:18Z
dc.identifier.eissn
1949-2553
dc.journal.volume
7
dc.journal.number
50
dc.journal.pagination
81995-82012
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Nueva York
dc.description.fil
Fil: Spender, Lindsay C.. University of Dundee; Reino Unido. The Beatson Institute for Cancer Research; Reino Unido
dc.description.fil
Fil: Ferguson, John. The Beatson Institute for Cancer Research; Reino Unido. MedImmune Limited; Reino Unido
dc.description.fil
Fil: Liu, Sijia. Leiden University; Países Bajos
dc.description.fil
Fil: Cui, Chao. Leiden University; Países Bajos
dc.description.fil
Fil: Girotti, Maria Romina. University of Manchester; Reino Unido. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil
Fil: Sibbet, Gary. The Beatson Institute for Cancer Research; Reino Unido
dc.description.fil
Fil: Higgs, Ellen. University of Dundee; Reino Unido
dc.description.fil
Fil: Shuttleworth, Morven K.. University of Dundee; Reino Unido
dc.description.fil
Fil: Hamilton, Tom. The Beatson Institute for Cancer Research; Reino Unido
dc.description.fil
Fil: Lorigan, Paul. University of Manchester; Reino Unido
dc.description.fil
Fil: Weller, Michael. Universitat Zurich; Suiza
dc.description.fil
Fil: Vincent, David F.. The Beatson Institute for Cancer Research; Reino Unido
dc.description.fil
Fil: Sansom, Owen J.. The Beatson Institute for Cancer Research; Reino Unido
dc.description.fil
Fil: Frame, Margaret. University of Edinburgh; Reino Unido
dc.description.fil
Fil: Dijke, Peter ten. Leiden University; Países Bajos
dc.description.fil
Fil: Marais, Richard. University of Manchester; Reino Unido
dc.description.fil
Fil: Inman, Gareth J.. The Beatson Institute for Cancer Research; Reino Unido. University of Dundee; Reino Unido
dc.journal.title
Oncotarget
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5b%5d=13226
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.18632/oncotarget.13226
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347669/
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/pmid/27835901