Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1995687 | Molecular Aspects of Medicine | 2015 | 416 Pages |
Abstract
Retinoic acid (RA), the major bioactive metabolite of retinol or vitamin A, induces a spectrum of pleiotropic effects in cell growth and differentiation that are relevant for embryonic development and adult physiology. The RA activity is mediated primarily by members of the retinoic acid receptor (RAR) subfamily, namely RARα, RARβ and RARγ, which belong to the nuclear receptor (NR) superfamily of transcription factors. RARs form heterodimers with members of the retinoid X receptor (RXR) subfamily and act as ligand-regulated transcription factors through binding specific RA response elements (RAREs) located in target genes promoters. RARs also have non-genomic effects and activate kinase signaling pathways, which fine-tune the transcription of the RA target genes. The disruption of RA signaling pathways is thought to underlie the etiology of a number of hematological and non-hematological malignancies, including leukemias, skin cancer, head/neck cancer, lung cancer, breast cancer, ovarian cancer, prostate cancer, renal cell carcinoma, pancreatic cancer, liver cancer, glioblastoma and neuroblastoma. Of note, RA and its derivatives (retinoids) are employed as potential chemotherapeutic or chemopreventive agents because of their differentiation, anti-proliferative, pro-apoptotic, and anti-oxidant effects. In humans, retinoids reverse premalignant epithelial lesions, induce the differentiation of myeloid normal and leukemic cells, and prevent lung, liver, and breast cancer. Here, we provide an overview of the biochemical and molecular mechanisms that regulate the RA and retinoid signaling pathways. Moreover, mechanisms through which deregulation of RA signaling pathways ultimately impact on cancer are examined. Finally, the therapeutic effects of retinoids are reported.
Keywords
CDKHSCHER2lncRNANCoRSCCDBDLBDEToAPLORFTCrWBCERKHDACCTDBCCPMLMDSLBPSRCRAEPRCAF-2AF-1PPARHMWPRBpKaSIRTsirtuinAP-1CRALBPAIDAITDPARPRBPCCR4PcGRetinoid X receptorDnmtHREHDMNTDPLZFRCCVDRIRBPDAXXRARRXRVPAncRNAsteroid receptor co-activatorPTCH1HNSCCSTAT5CTCLNMSCBCORhMTFABP5KLFPHFFLT3BRD4NPMPRAMECRBPTFIIHSMRTASXL1CYP26Nup98Am80NUMAPRKAR1ATFIIDNCOAFDACD437RBCCCRABP1rargTRAP220AMLHRAR9-cis-RADNA methyl-transferasenuclear mitotic apparatus proteinTBL1RNA polymerase II13-cis retinoic acid4-HPR5′-UTRHCCMAPKN-(4-Hydroxyphenyl)retinamidexeroderma pigmentosumnoncoding RNAv-akt murine thymoma viral oncogene homolog 1all-trans retinoic acidALKAktAcitretinNon-genomic effectsU.S. Food and Drug Administration9-cis Retinoic AcidOctinterferonIFNinterleukinBortezomibTriiodothyronineDifferentiationinternal tandem duplicationdirect repeatinverted repeatligand-binding pocketorganic cation transporter 1C-terminal domainN-terminal domainDNA binding domainligand binding domainRALDHRetinaldehyde dehydrogenaseRetinoidsRetinoic acidDevelopmentTranscriptionStructureCancerNSCLCbreast cancer 1, early onsetNon-melanoma skin cancerES cellHematopoietic stem cellEmbryonic stem cellNK cellsNatural killer cellsSézary syndromemyelodysplastic syndromeextracellular signal regulated kinaseSignalingLong noncoding RNAKrüppel-like factorHormone response elementVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)Chicken ovalbumin upstream promoter-transcription factorsignal transducer and activator of transcription 5open reading frameMycosis fungoidesCutaneous T-cell lymphomaleukemiaacute myeloid leukemiaMixed lineage leukemiaAPL, acute promyelocytic leukemiaretinol activity equivalents5′-untranslated regionMultiple myelomaTAFMicroRNAMiRNARARERaranucleophosminhistone acetyl-transferasehistone deacetylasehistone demethylaseValproic acidTATA box binding proteinactivator protein-1Promyelocytic leukemia proteinretinol binding proteinprotein kinase Amitogen-activated protein kinasePol IIpoly (ADP-ribose) polymeraseSingle nucleotide polymorphismCancer preventionSNPVADBRCA1non-small-cell lung carcinomaBasal cell carcinomaSquamous cell carcinomaHead and neck squamous cell carcinomaRenal cell carcinomaHepatocellular carcinomaKeratinKrtHATCOUP-TFcyclin-dependent kinasepolycomb groupwhite blood cellsEstrogen receptorRetinoic acid receptorThyroid receptorperoxisome proliferator-activated receptorT-cell receptornuclear receptor co-repressorVitamin D receptorHuman epidermal growth factor receptor-2Nuclear receptor
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Authors
Alessandra di Masi, Loris Leboffe, Elisabetta De Marinis, Francesca Pagano, Laura Cicconi, Cécile Rochette-Egly, Francesco Lo-Coco, Paolo Ascenzi, Clara Nervi,