title: Interplay between YB-1 and IL-6 promotes the metastatic phenotype in breast cancer cells.
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.
authors.affiliation: Molecular Pathology, Vall d'Hebron Research Institute (VHIR), Universidad Autonoma of Barcelona, Barcelona, Spain.|Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Bàrbara
authors.initials: B
authors.lastname: Castellana
authors.affiliation: Molecular Pathology, Vall d'Hebron Research Institute (VHIR), Universidad Autonoma of Barcelona, Barcelona, Spain.
authors.forename: Trond
authors.initials: T
authors.lastname: Aasen
authors.affiliation: Instituto de Investigaciones Biomédicas "Alberto Sols" CSIC-UAM, Madrid, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Moreno-Bueno
authors.affiliation: Phoenix Molecular Diagnostics Ltd., Richmond, BC, Canada.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Dunn
authors.affiliation: Molecular Pathology, Vall d'Hebron Research Institute (VHIR), Universidad Autonoma of Barcelona, Barcelona, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Ramón y Cajal
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D025461:Feedback, Physiological; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D009362:Neoplasm Metastasis; D010641:Phenotype; D010766:Phosphorylation; D034622:RNA Interference; D015398:Signal Transduction; D014162:Transfection; D051840:Y-Box-Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human
keywords: Y-box binding protein 1; breast cancer; interleukin-6; invasion; migration