Abstract 1053: Interplay of YB-1 and IL-6 in the acquisition of EMT-like characteristics

Abstract

Abstract An important step towards tumor progression and metastasis is the activation of the epithelial-mesenchymal transition (EMT) program. This complex process confers cancer cells traits such as enhanced motility, invasiveness and resistance to therapy. EMT can be triggered by the convergence of intrinsic factors and signals from the tumor microenvironment, such as aberrant expression of cytokines. Recently, the multifunctional oncoprotein YB-1 has been shown to play an important role in malignant tumors facilitating many of the “hallmarks of cancer” proposed by Hanahan and Weinberg. In this project we focused on the alliance between YB-1 and the cytokine IL-6, which has been implicated in tumor-cell metastasis and is a well known EMT inducer. Overexpression or direct addition of IL-6 up-regulates and activates YB-1 in the epithelial breast cancer cell line MCF7, leading to an upregulation of mesenchymal markers (Snail1, N-cadherin), increased cell migration and invasion, as well as morphological changes associated with an EMT-like phenotype. Conversely, in the mesenchymal-like breast cancer cell line MDA-MB-231, RNAi-mediated downregulation of YB-1 resulted in decreased IL-6 expression and an increase in epithelial-like cell characteristics. Our results describe a novel interplay whereby IL-6 regulates YB-1 and vice versa creating a positive feed-forward loop driving EMT during breast cancer progression. In the future we aim to delineate the exact signalling pathways linking IL-6 and YB-1, and how they converge to orchestrate important processes such as growth, invasion and metastasis. The understanding of this interplay will set the stage for new combinatorial treatments of aggressive breast cancers. Acronyms: EMT, epithelial to mesenchymal transition; YB-1, Ybox binding protein-1; IL-6 , Interleukin-6. Citation Format: Barbara Castellana, Trond Aasen, Santiago Ramón y Cajal. Interplay of YB-1 and IL-6 in the acquisition of EMT-like characteristics. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1053. doi:10.1158/1538-7445.AM2014-1053