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http://hdl.handle.net/2445/120306
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DC Field | Value | Language |
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dc.contributor.author | Garcia Recio, Susana | - |
dc.contributor.author | Pastor Arroyo, Eva M. | - |
dc.contributor.author | Marín Aguilera, Mercedes | - |
dc.contributor.author | Almendro Navarro, Vanessa | - |
dc.contributor.author | Gascón, Pere | - |
dc.date.accessioned | 2018-02-27T18:22:16Z | - |
dc.date.available | 2018-02-27T18:22:16Z | - |
dc.date.issued | 2015-06-26 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | http://hdl.handle.net/2445/120306 | - |
dc.description.abstract | BACKGROUND: Substance P (SP) is a pleiotropic cytokine/neuropeptide that enhances breast cancer (BC) aggressiveness by transactivating tyrosine kinase receptors like EGFR and HER2. We previously showed that SP and its cognate receptor NK-1 (SP/NK1-R) signaling modulates the basal phosphorylation of HER2 and EGFR in BC, increasing aggressiveness and drug resistance. In order to elucidate the mechanisms responsible for NK-1R-mediated HER2 and EGFR transactivation, we investigated the involvement of c-Src (a ligand-independent mediator) and of metalloproteinases (ligand-dependent mediators) in HER2/EGFR activation. RESULTS AND DISCUSSION: Overexpression of NK-1R in MDA-MB-231 and its chemical inhibition in SK-BR-3, BT-474 and MDA-MB-468 BC cells significantly modulated c-Src activation, suggesting that this protein is a mediator of NK-1R signaling. In addition, the c-Src inhibitor 4-(4'-phenoxyanilino)-6,7-dimethoxyquinazoline prevented SP-induced activation of HER2. On the other hand, SP-dependent phosphorylation of HER2 and EGFR decreased substantially in the presence of the MMP inhibitor 1-10, phenanthroline monohydrate, and the dual inhibition of both c-Src and MMP almost abolished the activation of HER2 and EGFR. Moreover, the use of these inhibitors demonstrated that this Src and MMP-dependent signaling is important to the cell viability and migration capacity of HER2+ and EGFR+ cell lines. CONCLUSION: Our results indicate that the transactivation of HER2 and EGFR by the pro-inflammatory cytokine/neuropeptide SP in BC cells is a c-Src and MMP-dependent process. | - |
dc.format.extent | 15 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Public Library of Science (PLoS) | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0129661 | - |
dc.relation.ispartof | PLoS One, 2015, vol. 10, num. 6, p. e0129661 | - |
dc.relation.uri | https://doi.org/10.1371/journal.pone.0129661 | - |
dc.rights | cc-by (c) Garcia Recio, Susana et al., 2015 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Medicina) | - |
dc.subject.classification | Càncer de mama | - |
dc.subject.classification | Genètica molecular | - |
dc.subject.classification | Metal·loproteïnes | - |
dc.subject.other | Breast cancer | - |
dc.subject.other | Molecular genetics | - |
dc.subject.other | Metalloproteins | - |
dc.title | The transmodulation of HER2 and EGFR by Substance P in breast cancer cells requires c-Src and metalloproteinase activation. | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 677098 | - |
dc.date.updated | 2018-02-27T18:22:16Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 26114632 | - |
Appears in Collections: | Articles publicats en revistes (Medicina) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) |
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677098.pdf | 2.88 MB | Adobe PDF | View/Open |
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