Confusingly, the cellular process autophagy (essentially self-eating) has been implicated in both cancer cell death and survival. New insight into this paradox has now been provided by the work of Robert Bast Jr. and colleagues, at the University of Texas MD Anderson Cancer Center, Houston, which indicates that the context in which the process occurs determines the outcome.
Expression of the gene ARHI is lost or downregulated in most cases of ovarian cancer. In the study, in vitro re-expression of ARHI in multiple human ovarian cancer cell lines induced autophagy and cell death.
However, when one of these cells lines was transplanted into mice as a xenograft, multiple factors within the tumor environment turned ARHI-induced autophagy into a mechanism of tumor cell survival, leading to tumor dormancy.
In addition to providing insight into the paradox that autophagy is associated with both cancer cell death and survival, the authors suggest that the data might provide new therapeutic approaches for the treatment of cancer.
Ravi Amaravadi, at the University of Pennsylvania, Philadelphia, discusses this further in an accompanying commentary.
- Lu et al. The tumor suppressor gene ARHI regulates autophagy and tumor dormancy in human ovarian cancer cells. Journal of Clinical Investigation, 2008; DOI: 10.1172/JCI35512
- Amaravadi et al. Autophagy-induced tumor dormancy in ovarian cancer. Journal of Clinical Investigation, 2008; DOI: 10.1172/JCI37667
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