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http://hdl.handle.net/2445/168553
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DC Field | Value | Language |
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dc.contributor.author | Rodriguez-Barrueco, Ruth | - |
dc.contributor.author | Yu, Jiyang | - |
dc.contributor.author | Saucedo-Cuevas, Laura P. | - |
dc.contributor.author | Olivan Riera, Mireia | - |
dc.contributor.author | Llobet-Navas, David | - |
dc.contributor.author | Putcha, Preeti | - |
dc.contributor.author | Castro, Verónica | - |
dc.contributor.author | Murga-Penas, Eva M. | - |
dc.contributor.author | Collazo-Lorduy, Ana | - |
dc.contributor.author | Castillo Martin, Mireia | - |
dc.contributor.author | Álvarez, Mariano | - |
dc.contributor.author | Cordon Cardo, Carlos | - |
dc.contributor.author | Kalinsky, Kevin | - |
dc.contributor.author | Maurer, Matthew | - |
dc.contributor.author | Califano, Andrea | - |
dc.contributor.author | Silva, José | - |
dc.date.accessioned | 2020-07-14T09:44:31Z | - |
dc.date.available | 2020-07-14T09:44:31Z | - |
dc.date.issued | 2015-08-01 | - |
dc.identifier.issn | 0890-9369 | - |
dc.identifier.uri | http://hdl.handle.net/2445/168553 | - |
dc.description.abstract | HER2-positive (HER2(+)) breast adenocarcinomas are a heterogeneous group in which hormone receptor (HR) status influences therapeutic decisions and patient outcome. By combining genome-wide RNAi screens with regulatory network analysis, we identified STAT3 as a critically activated master regulator of HR(-)/HER2(+) tumors, eliciting tumor dependency in these cells. Mechanistically, HR(-)/HER2(+) cells secrete high levels of the interleukin-6 (IL-6) cytokine, inducing the activation of STAT3, which in turn promotes a second autocrine stimulus to increase S100A8/9 complex (calprotectin) production and secretion. Increased calprotectin levels activate signaling pathways involved in proliferation and resistance. Importantly, we demonstrated that inhibition of the IL-6-Janus kinase 2 (JAK2)-STAT3-calprotectin axis with FDA-approved drugs, alone and in combination with HER2 inhibitors, reduced the tumorigenicity of HR(-)/HER2(+) breast cancers, opening novel targeted therapeutic opportunities. | - |
dc.format.extent | 18 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Cold Spring Harbor Laboratory Press | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1101/gad.262642.115 | - |
dc.relation.ispartof | Genes & Development, 2015, vol. 29, num. 15, p. 1631-1648 | - |
dc.relation.uri | https://doi.org/10.1101/gad.262642.115 | - |
dc.rights | (c) Rodriguez-Barrueco, Ruth et al., 2015 | - |
dc.source | Articles publicats en revistes (Patologia i Terapèutica Experimental) | - |
dc.subject.classification | Càncer de mama | - |
dc.subject.classification | Expressió gènica | - |
dc.subject.classification | Factors de transcripció | - |
dc.subject.other | Breast cancer | - |
dc.subject.other | Gene expression | - |
dc.subject.other | Transcription factors | - |
dc.title | Inhibition of the autocrine IL-6-JAK2-STAT3-calprotectin axis as targeted therapy for HR-/HER2+ breast cancers | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 694959 | - |
dc.date.updated | 2020-07-14T09:44:32Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 26227964 | - |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) |
Files in This Item:
File | Description | Size | Format | |
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694959.pdf | 893.59 kB | Adobe PDF | View/Open |
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