Interplay between YB-1 and IL-6 promotes the metastatic phenotype in breast cancer cells
Publisher
Impact JournalsDate
2015-01-01Citation
10.18632/oncotarget.5664
Oncotarget 6.35 (2015): 38239-38256
ISSN
1949-2553DOI
10.18632/oncotarget.5664Funded by
This work was supported by Fondo de Investigaciones Sanitarias (11/00185) and Redes Temáticas de Investigación Cooperativa en Salud (Ref. RD06/0020/1020). SRC acknowledges support from Generalitat de Catalunya (Ref. 2005SGR00144) and Fundación Mutua Madrileña (FMMA/2009/02). TA acknowledges support from Instituto de Salud Carlos III grant PI13/00763 and grant CP10/00624, co-financed by the European Regional Development Fund (ERDF)Editor's Version
http://dx.doi.org/10.18632/oncotarget.5664Subjects
Breast cancer; Y-box binding protein; Interleukin-6; Invasion; Migration; MedicinaAbstract
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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Google Scholar:Castellana, Bàrbara
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Aasen, Trond
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Moreno Bueno, Gema
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Dunn, Sandra E.
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Cajal, Santiago Ramón
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