Nuclear receptors: Lipid and hormone sensors with essential roles in the control of cancer development
Nuclear receptors (NRs) are a superfamily of ligand-activated transcription factors that act as biological sensors and use a combination of mechanisms to modulate positively and negatively gene expression in a spatial and temporal manner. The highly orchestrated biological actions of several NRs influence the proliferation, differentiation, and apoptosis of many different cell types. Synthetic ligands for several NRs have been the focus of extensive drug discovery efforts for cancer intervention. This review summarizes the roles in tumour growth and metastasis of several relevant NR family members, namely androgen receptor (AR), estrogen receptor (ER), glucocorticoid receptor (GR), thyroid hormone receptor (TR), retinoic acid receptors (RARs), retinoid X receptors (RXRs), peroxisome proliferator-activated receptors (PPARs), and liver X receptors (LXRs). These studies are key to develop improved therapeutic agents based on novel modes of action with reduced side effects and overcoming resistance. ; This work was supported by grants from the Spanish Ministry of Economy and Competitivity (MINECO) to AFV and CC (SAF201789510R) , to AA (SAF201783289R) , to MV (SAF201784934R) , to PP (SAF201788046R) , to EE (BFU201786906R) , and to the NuRCaMeIn network (SAF201790604REDT) ; grants from the Spanish Ministry of Science, Innovation and Universities (MCNU) and Fondo Europeo de Desarrollo Regional (FEDER) to MR (RTI2018-095928-B100) and AC (PID2019104284RBI00/AEI/10.13039/501100011033) ; a grant from Instituto de Salud Carlos IIIto AA (CIBERONC CB/16/00228) ; grants from the Autonomous Community of Madrid to AA (B2017/BMD-3724) and MR (MOIRB2017/BMD3684) ; grants from Fundacio La Marato de TV3 to CC (20160530) , AFV (201605-31) and MR (20160532) ; a grant from the Government of the Autonomous Community of Basque Country, Department of Industry, Tourism and Trade to MV (Elkartek, KK-2018/00054) ; and a grant from La Caixa to EEP (CaixaImpulseCI0018) . JFD received a fellowship from the Spanish Ministry of Science, ...