title: DNA damage and tumor surveillance: one trigger for two pathways.
abstract: Biological evolution ensures that several backup mechanisms always exist to prevent the failure of cellular processes of critical importance for life. This notion applies to processes aimed at preventing cancer development. Recent research suggests that the DNA damage response, activated in one of the earliest cellular responses to transformation, may elicit two independent tumor surveillance mechanisms. The first, and most well known, is activation of the proapoptotic molecule p53 and subsequent cellular suicide. The second, reported in a recent study, is induction of the expression of ligands for the activating immune receptor NKG2D. That DNA damage induces two independent tumor surveillance responses demonstrates how one tumor surveillance mechanism may be assisted by another to secure efficient protection against early tumorigenesis. The results also support the immunosurveillance theory of cancer and suggest that it may operate at very early stages of tumorigenesis.
authors.affiliation: Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden. petter.hoglund@mtc.ki.se
authors.forename: Petter
authors.initials: P
authors.lastname: Höglund
mesh_terms: D000818:Animals; D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000502:physiology; D006801:Humans; D006965:Hyperplasia; D007153:Immunologic Deficiency Syndromes / Q000150:complications; D007157:Immunologic Surveillance / Q000502:physiology*; D008024:Ligands; D008168:Lung / Q000473:pathology; D051379:Mice; D018448:Models, Immunological; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009369:Neoplasms / Q000235:genetics / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D011494:Protein Kinases / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology; D055607:Receptors, Natural Killer Cell; D015398:Signal Transduction / Q000502:physiology*; D016038:Skin Transplantation / Q000473:pathology; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; C578633:Chek2 protein, mouse; D017346:Protein Serine-Threonine Kinases