Breast cancer cells, which have disseminated to other organs and lie dormant, undergo autophagy to ensure their prolonged survival, according to a study in Nature Communications this week.
Cancer recurrence after initial diagnosis and treatment is a major cause of breast cancer mortality, which results from the metastatic outbreak of dormant tumour cells. However, the processes involved in the long-term survival of dormant breast cancer cells are largely unknown. Autophagy is a fundamental mechanism in which cells can self-repair by breaking down some of the tired cellular contents and replacing them with recycled components.
Kent Hunter and colleagues show that breast cancer cells that have spread engage autophagy to hibernate and survive in other organs. The authors show in 3D cell and mouse models that blocking autophagy by genetic manipulation and pharmacological inhibitors in these dormant, disseminated breast cancer cells impede their survival, leading to reduced tumour growth in distant organs. Mechanistically, they show that the reduced ability for tumour cells to survive upon autophagy inhibition is due to the accumulation of damaged mitochondria and oxidative stress, resulting in cell death.
The authors suggest that targeting autophagy may have therapeutic potential to prevent breast cancer recurrence.