Interplay between YB-1 and IL-6 promotes the metastatic phenotype in breast cancer cells
Castellana, Barbara (Departments of Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia)
Aasen, Trond (Hospital Universitari Vall d'Hebron)
Moreno-Bueno, Gema (Instituto de Investigaciones Biomédicas "Alberto Sols")
Dunn, Sandra E. (Phoenix Molecular Diagnostics Ltd., Richmond)
Ramón y Cajal, Santiago (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona

Fecha:	2015
Resumen:	Epithelial to mesenchymal transition (EMT) induces cell plasticity and promotes metastasis. The multifunctional oncoprotein Y-box binding protein-1 (YB-1) and the pleiotropic cytokine interleukin 6 (IL-6) have both been implicated in tumor cell metastasis and EMT, but via distinct pathways. Here, we show that direct interplay between YB-1 and IL-6 regulates breast cancer metastasis. Overexpression of YB-1 in breast cancer cell lines induced IL-6 production while stimulation with IL-6 increased YB-1 expression and YB-1 phosphorylation. Either approach was sufficient to induce EMT features, including increased cell migration and invasion. Silencing of YB-1 partially reverted the EMT and blocked the effect of IL-6 while inhibition of IL-6 signaling blocked the phenotype induced by YB-1 overexpression, demonstrating a clear YB-1/IL-6 interdependence. Our findings describe a novel signaling network in which YB-1 regulates IL-6, and vice versa, creating a positive feed-forward loop driving EMT-like metastatic features during breast cancer progression. Identification of signaling partners or pathways underlying this co-dependence may uncover novel therapeutic opportunities.
Ayudas:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2005/SGR-00144 Instituto de Salud Carlos III PI13-00763 Instituto de Salud Carlos III CP10/00624
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Y-box binding protein 1 ; Interleukin-6 ; Breast cancer ; Invasion ; Migration
Publicado en:	Oncotarget, Vol. 6 (october 2015) , p. 38239-38256, ISSN 1949-2553

DOI: 10.18632/oncotarget.5664
PMID: 26512918

18 p, 2.6 MB

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