Interplay between YB-1 and IL-6 promotes the metastatic phenotype in breast cancer cells |
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Authors: | Bàrbara Castellana Trond Aasen Gema Moreno-Bueno Sandra E. Dunn Santiago Ramón y Cajal |
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Affiliation: | 1. Molecular Pathology, Vall d''Hebron Research Institute (VHIR), Universidad Autonoma of Barcelona, Barcelona, Spain;2. Departments of Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada;3. Instituto de Investigaciones Biomédicas “Alberto Sols” CSIC-UAM, Madrid, Spain;4. Phoenix Molecular Diagnostics Ltd., Richmond, BC, Canada |
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Abstract: | 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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Keywords: | Y-box binding protein 1 interleukin-6 breast cancer invasion migration |
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