title: Uncoupling nuclear receptor LXR and cholesterol metabolism in cancer.
abstract: Liver X receptors (LXRs) are members of the nuclear receptor superfamily of DNA-binding transcription factors and act as sensors of cholesterol homeostasis. Under normal conditions, when intracellular cholesterol concentration increases, cells synthesize oxysterols and activate the LXR transcriptional network to drive cholesterol efflux and reduce cholesterol influx and synthesis. During normal and cancer cell proliferation, there is a net uncoupling between intracellular cholesterol increase and LXR activation resulting from the reduced intracellular oxysterol concentration. This review dissects the novel mechanisms of a previously unrecognized metabolic uncoupling, supporting the activation of the LXR axis as a bona fide therapeutic approach in cancer.
authors: Clinica Medica Cesare Frugoni, Dipartimento Interdisciplinare di Medicina, University of Bari Aldo Moro, 70124 Bari, Italy; National Cancer Institute, IRCCS Istituto Oncologico Giovanni Paolo II, 70124 Bari, Italy.
authors: Fabiola
authors: F
authors: Bovenga
authors: Clinica Medica Cesare Frugoni, Dipartimento Interdisciplinare di Medicina, University of Bari Aldo Moro, 70124 Bari, Italy.
authors: Carlo
authors: C
authors: Sabbà
authors: Clinica Medica Cesare Frugoni, Dipartimento Interdisciplinare di Medicina, University of Bari Aldo Moro, 70124 Bari, Italy; National Cancer Institute, IRCCS Istituto Oncologico Giovanni Paolo II, 70124 Bari, Italy. Electronic address: antonio.moschetta@uniba.it.
authors: Antonio
authors: A
authors: Moschetta
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000502:physiology; D000071518:Liver X Receptors; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000187:drug effects / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology; D059467:Transcriptome
chemical_list: D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D002784:Cholesterol