Immune system contribution to tumor heterogeneity may influence liver cancer growth
Ross Weber, a graduate student in Birsoy's lab, made the discovery after he reduced cells' lysosomal acidity enough to stress the cells, but not kill them. In responding to this challenge, the cells activated genes involved in the use of iron, while their iron levels dramatically dropped.
Cells don't cope for long without iron, which is needed to make DNA and other essential molecules. When a rise in pH causes iron depletion, cells stop dividing and eventually die. The scientists think this happens because lysosomes free iron from the molecules that transport it, something they do best at a pH of 4 to 5, the approximate acidity of a tomato.
Because lysosomes are known to be essential for cancer-cell proliferation, the discovery suggests a potentially new way to fight tumors: starving them for iron. In recent years, Birsoy's lab has devised a number of innovative ways to kill cancer cells by blocking their access to essential nutrients; now iron depletion promises to yield yet another weapon in this arsenal of potential drugs.
In the future, it will be important to determine whether these findings are also relevant in the context of other conditions linked to the loss of acidity, such as lysosomal storage disorders and neurodegenerative diseases. We believe there are a lot of exciting possibilities out there." Kivanç Birsoy, Chapman Perelman Assistant Professor at The Rockefeller University Source:
Rockefeller University Journal reference:
Weber, R. A., et al. (2020) Maintaining Iron Homeostasis Is the Key Role of Lysosomal Acidity for Cell Proliferation. Molecular Cell . doi.org/10.1016/j.molcel.2020.01.003 .
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