Autophagy and tumor suppression: recent advances in understanding the link between autophagic cell death pathways and...

Autophagy is a process by which the cell recycles its components through self-consumption of cellular organelles and bulk cytoplasm. In times of stress, it serves to generate much needed nutrients. When overactivated, however, the orderly destruction of organelles can lead to cell death. At times, autophagic cell death is used as an alternative to apoptosis to eliminate unwanted, damaged, or transformed cells. Consistent with this, tumorigenesis is associated with a downregulation in autophagy, and genes that mediate the execution of the process have been shown to be tumor suppressors. At the same time, basal autophagy has been harnessed by some tumor cells as a survival mechanism to protect against ischemia and signals that induce apoptosis. Thus, the relationship between autophagy and tumor development is complex. Here, we discuss the basic machinery of mammalian autophagy and its regulators, with specific emphasis on those genes that have been linked to cancer. Research supporting the divergent nature of autophagy in both tumor suppression and tumor progression is presented. We conclude with a survey of recent approaches to treating cancer with strategies that modulate autophagy.