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Oncotarget. 2015 Nov 10;6(35):38239-56. doi: 10.18632/oncotarget.5664.

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

Author information

1
Molecular Pathology, Vall d'Hebron Research Institute (VHIR), Universidad Autonoma of Barcelona, Barcelona, Spain.
2
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.

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.

KEYWORDS:

Y-box binding protein 1; breast cancer; interleukin-6; invasion; migration

PMID:
26512918
PMCID:
PMC4741996
DOI:
10.18632/oncotarget.5664
[Indexed for MEDLINE]
Free PMC Article

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