Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10895540 | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer | 2016 | 38 Pages |
Abstract
One of the hallmarks of cancer is resistance to programmed cell death, which maintains the survival of cells en route to oncogenic transformation and underlies therapeutic resistance. Recent studies demonstrate that programmed cell death is not confined to caspase-dependent apoptosis, but includes necroptosis, a form of necrotic death governed by Receptor-Interacting Protein 1 (RIP1), RIP3, and Mixed Lineage Kinase Domain-Like (MLKL) protein. Necroptosis serves as a critical cell-killing mechanism in response to severe stress and blocked apoptosis, and can be induced by inflammatory cytokines or chemotherapeutic drugs. Genetic or epigenetic alterations of necroptosis regulators such as RIP3 and cylindromatosis (CYLD), are frequently found in human tumors. Unlike apoptosis, necroptosis elicits a more robust immune response that may function as a defensive mechanism by eliminating tumor-causing mutations and viruses. Furthermore, several classes of anticancer agents currently under clinical development, such as SMAC and BH3 mimetics, can promote necroptosis in addition to apoptosis. A more complete understanding of the interplay among necroptosis, apoptosis, and other cell death modalities is critical for developing new therapeutic strategies to enhance killing of tumor cells.
Keywords
IL-1αPGAM5terminal deoxynucleotidyl transferase mediated dUTP nick end labelingDCsTLRFADDHMGB1Drp1TNFSMACMCMVNSAHSV-1HCMVCLLRHIMdsRNAPTPnecrosulfonamide5-FUMLKLRIP1necrostatin-1PARP1DAMPsRIP3LPScIAPMAPKNec-1double-stranded RNAROSdamage associated molecular patternsAIFPermeability transition poreinterferonIFNInterleukin-1αTUNELToll-like receptorhigh-mobility group box 1Fas-associated death domainsecond mitochondria-derived activator of caspasesCancerDendritic cellsHuman cytomegalovirusMurine cytomegalovirusCyldCylindromatosisapoptosis-inducing factorphosphoglycerate mutase family member 5Fas LigandFasLtumor necrosis factor5-fluorouracilAcute lymphoblastic leukemiaChronic lymphocytic leukemiaLipopolysaccharidesmixed lineage kinase domain-likecellular inhibitor of apoptosis proteinNecroptosisNADknockoutnicotinamide adenine dinucleotideALLHerpes simplex virus 1RIPdynamin-related protein 1mitogen-activated protein kinaseReceptor-interacting proteinPoly(ADP-ribose) polymerase 1poly(I:C)polyinosinic-polycytidylic acidSingle nucleotide polymorphismSNPReactive oxygen species
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Authors
Dongshi Chen, Jian Yu, Lin Zhang,