Research Papers:

Interplay between YB-1 and IL-6 promotes the metastatic phenotype in breast cancer cells

Bàrbara Castellana _, Trond Aasen, Gema Moreno-Bueno, Sandra E. Dunn and Santiago Ramón y Cajal

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Oncotarget. 2015; 6:38239-38256. https://doi.org/10.18632/oncotarget.5664

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Bàrbara Castellana1,2, Trond Aasen1, Gema Moreno-Bueno3, Sandra E. Dunn4, Santiago Ramón y Cajal1

1Molecular Pathology, Vall d’Hebron Research Institute (VHIR), Universidad Autonoma of Barcelona, Barcelona, Spain

2Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada

3Instituto de Investigaciones Biomédicas “Alberto Sols” CSIC-UAM, Madrid, Spain

4Phoenix Molecular Diagnostics Ltd., Richmond, BC, Canada

Correspondence to:

Bàrbara Castellana, e-mail: [email protected]

Santiago Ramón y Cajal, e-mail: [email protected]

Keywords: Y-box binding protein 1, interleukin-6, breast cancer, invasion, migration

Received: April 11, 2015     Accepted: October 05, 2015     Published: October 15, 2015


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.

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