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http://hdl.handle.net/2445/172848
Title: | Snail mediates crosstalk between TGFβ and LXRα in hepatocellular carcinoma |
Author: | Bellomo, Claudia Caja Puigsubirà, Laia Fabregat Romero, Isabel Mikulits, Wolfgang Kardassis, Dimitris Heldin, Carl-Henrik Moustakas, Aristidis |
Keywords: | Càncer de fetge Terapèutica Liver cancer Therapeutics |
Issue Date: | 11-Dec-2017 |
Publisher: | Nature Publishing Group |
Abstract: | Understanding the complexity of changes in differentiation and cell survival in hepatocellular carcinoma (HCC) is essential for the design of new diagnostic tools and therapeutic modalities. In this context, we have analyzed the crosstalk between transforming growth factor β (TGFβ) and liver X receptor α (LXRα) pathways. TGFβ is known to promote cytostatic and pro-apoptotic responses in HCC, and to facilitate mesenchymal differentiation. We here demonstrate that stimulation of the nuclear LXRα receptor system by physiological and clinically useful agonists controls the HCC response to TGFβ. Specifically, LXRα activation antagonizes the mesenchymal, reactive oxygen species and pro-apoptotic responses to TGFβ and the mesenchymal transcription factor Snail mediates this crosstalk. In contrast, LXRα activation and TGFβ cooperate in enforcing cytostasis in HCC, which preserves their epithelial features. LXRα influences Snail expression transcriptionally, acting on the Snail promoter. These findings propose that clinically used LXR agonists may find further application to the treatment of aggressive, mesenchymal HCCs, whose progression is chronically dependent on autocrine or paracrine TGFβ. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41418-017-0021-3 |
It is part of: | Cell Death and Differentiation, 2017 |
URI: | http://hdl.handle.net/2445/172848 |
Related resource: | https://doi.org/10.1038/s41418-017-0021-3 |
ISSN: | 1350-9047 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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