Nucleotide metabolism, oncogene-induced senescence and cancer.
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.
Gene Expression and Regulation Program, The Wistar Institute Cancer Center, The Wistar Institute, Philadelphia, PA 19104, United States.
Katherine M
KM
Aird
Gene Expression and Regulation Program, The Wistar Institute Cancer Center, The Wistar Institute, Philadelphia, PA 19104, United States. Electronic address: rzhang@wistar.org.
Rugang
R
Zhang
D014408:Biomarkers, Tumor / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D003854:Deoxyribonucleotides / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism; D009857:Oncogenes / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
D014408:Biomarkers, Tumor; D003854:Deoxyribonucleotides
Cancer; Cancer therapy; DNA damage response; Nucleotide metabolism; Oncogene-induced senescence; Replication stress