Cholesterol plays an indispensable role in regulating the properties of cell membranes in mammalian cells. Accumulation of cholesterol and its intermediates, such as oxysterols, lead to activation of the nuclear receptors LXRs (liver X receptors). LXR is an important regulator of cholesterol homoeostasis by controlling its transport and its neo-synthesis. Accumulating evidence indicates that the endogenous ligands of LXRs, oxysterols, play an active and important role in regulating the fate and function of immune cells. Indeed, LXRs are negative regu-lators of innate immunity by interfering with macrophage activation. Recent advances have highlighted a controversial role for LXR in cancer. In this issue of the Biochemical Journal, Wang et al. propose that LXR agonist directly controls IFN-γ (interferon-γ) expression, which limits tumour growth. This protective effect mediated by LXR appears to be dependent on IFN-γ. Thus, despite accumulation of endogenous ligand of LXR in cancer, activation of LXR seems protective. This novel evidence provides a new perspective for targeting LXR in cancer, although controversial studies can be also found in the literature. In order to avoid side effects associated with LXR agonists, molecular and cellular studies are required to decipher this unexpected action of LXRs.
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April 2014
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March 28 2014
Liver X receptor: from metabolism to cancer
Nicolas Venteclef;
Nicolas Venteclef
*INSERM, UMR_S 1138, Cordeliers, F-75006 Paris, France
†Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Cordeliers, F-75006 Paris, France
‡Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Cordeliers, F-75006 Paris, France
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Pascal Ferré
Pascal Ferré
1
*INSERM, UMR_S 1138, Cordeliers, F-75006 Paris, France
†Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Cordeliers, F-75006 Paris, France
‡Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Cordeliers, F-75006 Paris, France
1To whom correspondence should be addressed (email pascal.ferre@crc.jussieu.fr).
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Publisher: Portland Press Ltd
Received:
February 14 2014
Accepted:
February 17 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 459 (2): e1–e3.
Article history
Received:
February 14 2014
Accepted:
February 17 2014
Connected Content
A commentary has been published:
Identification of interferon-γ as a new molecular target of liver X receptor
Citation
Nicolas Venteclef, Pascal Ferré; Liver X receptor: from metabolism to cancer. Biochem J 15 April 2014; 459 (2): e1–e3. doi: https://doi.org/10.1042/BJ20140211
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