Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10899769 | Cancer Letters | 2015 | 7 Pages |
Abstract
Senescence is defined as a stable cell growth arrest. Oncogene-induced senescence (OIS) occurs when an activated oncogene is expressed in a normal cell. OIS acts as a bona fide tumor suppressor mechanism by driving stable growth arrest of cancer progenitor cells harboring the initial oncogenic hit. OIS is often characterized by aberrant DNA replication and the associated DNA damage response. Nucleotides, in particular deoxyribonucleotide triphosphates (dNTPs), are necessary for both DNA replication and repair. Imbalanced dNTP pools play a role in a number of human diseases, including during the early stages of cancer development. This review will highlight what is currently known about the role of decreased nucleotide metabolism in OIS, how nucleotide metabolism leads to transformation and tumor progression, and how this pathway can be targeted as a cancer therapeutic by inducing senescence of cancer cells.
Keywords
WRNIMPdNTPHRASuridine monophosphateRRM2TTPNDPRNRE2F1BRAFv-raf murine sarcoma viral oncogene homolog BEOCUDPv-myc avian myelocytomatosis viral oncogene homologRECQL4OISataxia telangiectasia and Rad3-related protein3-APBLMCDKdNDPNTPATRneuroblastoma RAS viral (v-ras) oncogene homologNRASDDRNADPHshRNARASPRBUMPataxia telangiectasia mutatedBRCA1/2c-MycDNAshort hairpin RNAuridine diphosphatedeoxyribonucleic acidOncogene-Induced Senescencesenescence-associated beta-galactosidasedeoxyribonucleotide triphosphateReplication stressthymidine triphosphateATMRad51Ribonucleotide reductaseribonucleoside triphosphateCancerEpithelial ovarian cancerCancer therapythymidylate synthaseE2F transcription factor 1Nucleotide metabolismInosine monophosphatenicotinamide adenine dinucleotide phosphateHydroxyureaDNA damage responseretinoblastoma proteincyclin-dependent kinase
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Authors
Katherine M. Aird, Rugang Zhang,