The role of autophagy in tumour development and cancer therapy.
Autophagy is a catabolic membrane-trafficking process that leads to sequestration and degradation of intracellular material within lysosomes. It is executed at basal levels in every cell and promotes cellular homeostasis by regulating organelle and protein turnover. In response to various forms of cellular stress, however, the levels and cargoes of autophagy can be modulated. In nutrient-deprived states, for example, autophagy can be activated to degrade cargoes for cell-autonomous energy production to promote cell survival. In other contexts, in contrast, autophagy has been shown to contribute to cell death. Given these dual effects in regulating cell viability, it is no surprise that autophagy has implications in both the genesis and treatment of malignant disease. In this review, we provide a comprehensive appraisal of the way in which oncogenes and tumour suppressor genes regulate autophagy. In addition, we address the current evidence from human cancer and animal models that has aided our understanding of the role of autophagy in tumour progression. Finally, the potential for targeting autophagy therapeutically is discussed in light of the functions of autophagy at different stages of tumour progression and in normal tissues.
Rosenfeldt
Mathias T
MT
Tumour Cell Death Laboratory, Beatson Institute for Cancer Research, Glasgow, G61 1BD, UK.
Ryan
Kevin M
KM
D024221:Antineoplastic Protocols; D017209:Apoptosis / Q000235:genetics*; D001343:Autophagy / Q000235:genetics*; D016923:Cell Death; D002470:Cell Survival / Q000235:genetics; D003593:Cytoplasm; D006801:Humans; D009369:Neoplasms; D009857:Oncogenes / Q000235:genetics*; D010588:Phagosomes; D021381:Protein Transport / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics