Final Report Summary - CANCERPHAGY (Autophagy as a cancer treatment)
Autophagy is one of the major cellular degradation pathways and the only pathway that can degrade organelles. It is essential pathway for maintaining cellular homeostasis and its malfunctioning has implications in numerous diseases. We have investigated the role of autophagy in both tumour biology and ageing. Our work contributed to understanding of how enhancement of autophagy process improves health and extends lifespan in Drosophila. Importantly we showed that mild increase in autophagy is beneficial for health and delays ageing while, contrarily, strong autophagy increase is detrimental. Using well-established Drosophila tumour model, and a method to transplant tumours in flies, we demonstrated that mild autophagy increase slows tumour growth. We used transcriptomic and metabolomics approach to uncover alterations upon autophagy enhancement and showed pronounced immune response and down-regulation of lipid metabolism. Interestingly, we demonstrate that major differences between mild and strong autophagy increase are changes in mitochondrial gene expression. This is an important finding as we demonstrate that flies with autophagy alteration are resistant to mitochondrial toxins. Our work shed light on different outcomes when autophagy is increased, depending on the level of autophagy upregulation. We provide in depth characterisation how this intervention affects cellular metabolism and immunity. In addition we uncovered a role for slowing the tumour growth through autophagy increase in the tumour microenvironment. We have also used pharmacological approach to induce autophagy process and replicate our findings using rapamycin, torin, and lithium.
In sum, our results shed light on the role of autophagy on tumour growth and ageing, thereby opening many interesting possibilities to explore this further.
In sum, our results shed light on the role of autophagy on tumour growth and ageing, thereby opening many interesting possibilities to explore this further.