PMID: 22583411May 16, 2012Paper

The nuclear orphan receptors NR4A as therapeutic target in cancer therapy

Anti-cancer Agents in Medicinal Chemistry
Alexander J A DeutschPeter Neumeister

Abstract

NR4A1 (Nur77), NR4A2 (Nurr1) and NR4A3 (Nor-1) are three members of the orphan nuclear receptor (NR) family referred to as NR4A family. This subgroup activates gene expression in a constitutive ligand-independent manner. These nuclear receptors are classified as early response genes that are induced by a diverse range of signals. These orphan NRs have been implicated in cell cycle regulation, apoptosis, inflammation, metabolism and more recently in carcinogenesis. The ultimate growth of a tumor depends not only on the rate of tumor cell proliferation, but also the rate of apoptosis and NR4A1 controls both, survival and death of cancer cells. It has been demonstrated that NR4A1 activities are regulated through its subcellular localisation. In the nucleus, NR4A1 can function in a context dependent manner either as an oncogenic survival factor, promoting cancer cell growth or as the opposite through the activation of apoptosis. Additionally, in an atypical fashion, it is a potent killer when migrating to the mitochondria, where it binds to Bcl-2 and converts its survival phenotype, triggering cytochrome c release and apoptosis. The most convincing evidence that nuclear orphan receptors function as critical tumor suppressors is the...Continue Reading

Citations

Nov 30, 2015·Computers in Biology and Medicine·Mohammadmersad GhorbaniAnnette Payne
Jun 28, 2015·Prostaglandins & Other Lipid Mediators·Hongya HanHans-Erik Claesson
May 30, 2015·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·J GuoZ Wang
Mar 27, 2013·Journal of Receptor and Signal Transduction Research·Harmit S Ranhotra
Dec 30, 2014·Medical Hypotheses·Michael R Paillasse, Philippe de Medina
Dec 10, 2015·Journal of Molecular Endocrinology·Houssein S AbdouJacques J Tremblay
Oct 1, 2014·PloS One·Glenda EgerCarl-Henrik Heldin
Oct 26, 2016·Archives of Pharmacal Research·Hee Yeon Won, Eun Sook Hwang
Jun 28, 2013·Asian Pacific Journal of Cancer Prevention : APJCP·Jian WangZhi-Wei He
May 3, 2019·Journal of Cellular and Molecular Medicine·Linying SunYueran Zhao
Mar 3, 2017·Cancer Research·Alexander J A DeutschPeter Neumeister
Aug 27, 2021·Journal of Molecular Biology·Fatéma DodatDaniel Lévesque

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