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Snail mediates cros...
Snail mediates crosstalk between TGFβ and LXRα in hepatocellular carcinoma
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- Bellomo, Claudia (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Ludwiginstitutet för cancerforskning,Science for Life Laboratory, SciLifeLab
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- Caja, Laia (author)
- Uppsala universitet,Ludwiginstitutet för cancerforskning,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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- Fabregat, Isabel (author)
- Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, and Department of Physiological Sciences, School of Medicine, University of Barcelona, ES-08908, Barcelona, Spain
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- Mikulits, Wolfgang (author)
- Department of Medicine I, Division: Institute of Cancer Research, Comprehensive Cancer Center Vienna, Medical University of Vienna, A-1090, Vienna, Austria
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- Kardassis, Dimitris (author)
- Division of Basic Medical Sciences, University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology of Hellas, GR-71003, Heraklion, Greece
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- Heldin, Carl-Henrik, 1952- (author)
- Uppsala universitet,Ludwiginstitutet för cancerforskning,Science for Life Laboratory, SciLifeLab
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- Moustakas, Aristidis (author)
- Uppsala universitet,Ludwiginstitutet för cancerforskning,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2017-12-11
- 2018
- English.
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In: Cell Death and Differentiation. - : Springer Science and Business Media LLC. - 1350-9047 .- 1476-5403. ; 25:5, s. 885-903
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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