Anti-cancer therapies aimed at blocking mitochondrial energy generation may have wider effects on cancer cell behaviour than just preventing proliferation, new Cambridge research into brain development and tumours in the fruit fly suggests.
Cancer cells were once thought to rely on sugar as the primary fuel for their growth, a phenomenon known as the Warburg effect.
More recently, it has become clear that other energy sources may be equally important, and much of the growth in cancer cells is fuelled by mitochondria, the powerhouses of cells.
The role of mitochondrial energy generation by oxidative phosphorylation (OxPhos) in tumour growth has since attracted much attention as a potential therapeutic target for cancer.
In a new study published in eLife, comparing the roles of mitochondrial metabolism in normal brain development and in brain tumours, Jelle van den Ameele and Andrea Brand at the Wellcome Trust/ Cancer Research UK Gurdon Institute now show that mitochondria contribute to much more than cell proliferation and growth.
They studied the brains of fruit flies that, remarkably, can develop brain tumours that exhibit many of the hallmarks of human cancer. The researchers discovered that blocking the OxPhos pathway in mitochondria in neural stem cells and brain tumour cells not only reduces cell proliferation, but also limits the diversity of cell types they can generate.
Experimental therapies for cancer based on inhibiting OxPhos are currently being trialled. This new study now demonstrates that these therapies may have far wider effects on stem cell behaviour than simply preventing uncontrolled cell proliferation.
Cell diversity is essential in normal development and for tumour growth, explained first author and Research Associate, Dr Jelle van den Ameele.
At the base of these are the proliferating stem cells. Blocking mitochondrial function slows their growth and at the same time keeps more cells in a stem-cell state. These stem cells could later emerge to grow, metastasise and cause resistance to therapy.
A better understanding of the interactions between metabolism, normal brain cell growth, and the diversity of cell types in tumours, could uncover new therapeutic approaches.
The work was funded by the Wellcome Trust, Royal Society and European Molecular Biology Organization; and by core funding to the Gurdon Institute from the Wellcome Trust and Cancer Research UK.
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