NIH Research Festival
Stem cells have been identified in many normal adult organs and cancers. These cells are exceptionally resistant to attempts that kill regular cells and maybe the real culprit behind tumor recurrence after initial chemotherapy. However, very little is known about the properties of these cells. In this study, we investigated stem cell death in adult Drosophila digestion system. We found that activating apoptotic pathway selectively killed differentiated cells but not normal and transformed stem cells while the knockdowns of COPI/Arf1 complex selectively killed normal and transformed stem cells through necrosis, by attenuating the lipolysis pathway, but not differentiated cells. The dying stem cells were engulfed by neighboring differentiated cells through a Draper-Mbc/Rac1-JNK-dependent autophagy pathway. Furthermore, Arf1 inhibitors inhibit cancer stem cells in human cancer cell lines. Our results suggest that normal stem cells or cancer stem cells like hibernating animals may mainly rely on lipid reserves for energy supply and blocking of lipolysis can starve them to death. This finding may lead to design new therapies to selectively eliminate stem cells in cancer.
Scientific Focus Area: Stem Cell Biology
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