Liver X receptor: from metabolism to cancer

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 homoeos...

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Bibliographic Details
Published in:Biochemical journal Vol. 459; no. 2; p. e1
Main Authors: Venteclef, Nicolas, Ferré, Pascal
Format: Journal Article
Language:English
Published: England 15.04.2014
Subjects:
Animals
Cell Proliferation
Gene Expression Regulation - physiology
Humans
Immunologic Factors
Inflammation - metabolism
Interferon-gamma - genetics
Interferon-gamma - metabolism
Liver X Receptors
Neoplasms - metabolism
Orphan Nuclear Receptors - genetics
Orphan Nuclear Receptors - metabolism
Signal Transduction
Sterols - metabolism
ISSN:1470-8728, 1470-8728
Online Access:Get more information
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Summary: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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ISSN:1470-8728
1470-8728
DOI:10.1042/BJ20140211