Miniatura

Fitxers

694959.pdf (893.59 KB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2015-08-01

Tots els drets reservats

Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/168553

Inhibition of the autocrine IL-6-JAK2-STAT3-calprotectin axis as targeted therapy for HR-/HER2+ breast cancers

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1101/gad.262642.115

Resum

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.

Matèries

Càncer de mama, Expressió gènica, Factors de transcripció

Matèries (anglès)

Breast cancer, Gene expression, Transcription factors

Citació

Col·leccions

Articles publicats en revistes (Patologia i Terapèutica Experimental)

Citació

RODRIGUEZ-BARRUECO, Ruth, YU, Jiyang, SAUCEDO-CUEVAS, Laura p., OLIVAN RIERA, Mireia, LLOBET-NAVAS, David, PUTCHA, Preeti, CASTRO, Verónica, MURGA-PENAS, Eva m., COLLAZO-LORDUY, Ana, CASTILLO MARTIN, Mireia, ÁLVAREZ, Mariano, CORDON CARDO, Carlos, KALINSKY, Kevin, MAURER, Matthew, CALIFANO, Andrea, SILVA, José. Inhibition of the autocrine IL-6-JAK2-STAT3-calprotectin axis as targeted therapy for HR-/HER2+ breast cancers. _Genes & Development_. 2015. Vol. 29, núm. 15, pàgs. 1631-1648. [consulta: 27 de gener de 2026]. ISSN: 0890-9369. [Disponible a: https://hdl.handle.net/2445/168553]

Exportar metadades

JSON - METS

Compartir registre