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http://hdl.handle.net/2445/126441
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DC Field | Value | Language |
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dc.contributor.author | Vazquez Martin, Alejandro | - |
dc.contributor.author | Cufí, Sílvia | - |
dc.contributor.author | Oliveras Ferraros, Cristina | - |
dc.contributor.author | Torres Garcia, Violeta Zenobia | - |
dc.contributor.author | Corominas Faja, Bruna | - |
dc.contributor.author | Cuyàs, Elisabet | - |
dc.contributor.author | Bonavia, Rosa | - |
dc.contributor.author | Visa, Joana | - |
dc.contributor.author | Martin Castillo, Begoña | - |
dc.contributor.author | Barrajón Catalán, Enrique | - |
dc.contributor.author | Micol, Vicente | - |
dc.contributor.author | Bosch Barrera, Joaquim | - |
dc.contributor.author | Menendez, Javier A. | - |
dc.date.accessioned | 2018-11-26T14:29:24Z | - |
dc.date.available | 2018-11-26T14:29:24Z | - |
dc.date.issued | 2013-09-02 | - |
dc.identifier.uri | http://hdl.handle.net/2445/126441 | - |
dc.description.abstract | Using non-small cell lung carcinoma (NSCLC) cells harboring the erlotinib-sensitizing Epidermal Growth Factor Receptor (EGFR) exon 19 mutation delE746-A750, we developed erlotinib-refractory derivatives in which hyperactive Insulin-like Growth Factor-1 Receptor (IGF-1R) signaling associated with enrichment in epithelial-to-mesenchymal transition (EMT)-related morphological and transcriptional features. We then explored whether an IGF-1R/EMT crosstalk was sufficient to promote erlotinib refractoriness in the absence of second-site EGFR mutations, MET and AXL hyperactivation. Transforming Growth Factor-beta1 (TGF beta 1)-induced mesenchymal trans-differentiation was sufficient to impede erlotinib functioning in the presence of drug-sensitive delE746-A750 EGFR mutation. Pharmacological blockade of IGF-1R fully prevented the TGF beta 1's ability to activate an EMT protein signature [E-cadherin low/vimentin high]. The sole presence of erlotinib was capable of rapidly activate an IGF-1R-dependent, vimentin-enriched mesenchymal-like phenotype in delE746-A750-mutated epithelial cells. Even if transient, NSCLC cells' intrinsic plasticity to undergo crosstalk between IGF-1R and EMT signaling pathways can sufficiently eliminate the erlotinib-sensitizing effect of highly prevalent EGFR mutations and suggests the urgent need for dual IGF-1R/EMT-targeting strategies to circumvent erlotinib resistance. | - |
dc.format.extent | 15 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Nature Publishing Group | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1038/srep02560 | - |
dc.relation.ispartof | Scientific Reports, 2013, vol. 3 | - |
dc.relation.uri | https://doi.org/10.1038/srep02560 | - |
dc.rights | cc by (c) Vazquez Martin et al., 2013 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Càncer de pulmó | - |
dc.subject.other | Lung cancer | - |
dc.title | IGF-1R/epithelial-to-mesenchymal transition (EMT) crosstalk suppresses the erlotinib-sensitizing effect of EGFR exon 19 deletion mutations | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2018-07-24T12:46:26Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 23994953 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
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Vazquez-MartinA.pdf | 7.86 MB | Adobe PDF | View/Open |
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