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dc.contributor.authorRodriguez-Barrueco, Ruth-
dc.contributor.authorYu, Jiyang-
dc.contributor.authorSaucedo-Cuevas, Laura P.-
dc.contributor.authorOlivan Riera, Mireia-
dc.contributor.authorLlobet-Navas, David-
dc.contributor.authorPutcha, Preeti-
dc.contributor.authorCastro, Verónica-
dc.contributor.authorMurga-Penas, Eva M.-
dc.contributor.authorCollazo-Lorduy, Ana-
dc.contributor.authorCastillo Martin, Mireia-
dc.contributor.authorÁlvarez, Mariano-
dc.contributor.authorCordon Cardo, Carlos-
dc.contributor.authorKalinsky, Kevin-
dc.contributor.authorMaurer, Matthew-
dc.contributor.authorCalifano, Andrea-
dc.contributor.authorSilva, José-
dc.description.abstractHER2-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.extent18 p.-
dc.publisherCold Spring Harbor Laboratory Press-
dc.relation.isformatofReproducció del document publicat a:
dc.relation.ispartofGenes & Development, 2015, vol. 29, num. 15, p. 1631-1648-
dc.rights(c) Rodriguez-Barrueco, Ruth et al., 2015-
dc.subject.classificationCàncer de mama-
dc.subject.classificationExpressió gènica-
dc.subject.classificationFactors de transcripció-
dc.subject.otherBreast cancer-
dc.subject.otherGene expression-
dc.subject.otherTranscription factors-
dc.titleInhibition of the autocrine IL-6-JAK2-STAT3-calprotectin axis as targeted therapy for HR-/HER2+ breast cancers-
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)

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