Splicing DNA-damage responses to tumour cell death.
The ability of a tumour cell to evade programmed cell death (apoptosis) is crucial in the development of cancer. The process of apoptosis is complex and involves the careful interplay of a host of signalling molecules. Cellular stresses, such as DNA-damage, can initiate apoptosis through multiple pathways, all of which eventually lead to eradication of damaged cells that may otherwise go on to form a tumour. Moreover, the relevance of this to combating cancer is very strong since several therapeutic agents used to treat malignant disease utilize the cells' apoptotic machinery. The purpose of this review is to provide an insight into what we know about how apoptosis is initiated by DNA-damaging agents, how pro- and anti-apoptotic signals converge in the execution of cell death, and how such mechanisms can be perturbed in cancer.
Crighton
Diane
D
Tumour Cell Death Laboratory, Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Ryan
Kevin M
KM
D017209:Apoptosis / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics; D050684:E2F Transcription Factors; D016147:Genes, Tumor Suppressor; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D009857:Oncogenes; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D014157:Transcription Factors; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases