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Selenocysteine metabolism in cancer

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Selenium is a micronutrient that is required to produce selenoproteins, but is toxic at higher concentrations. We have found that due to their increased expression of the xCT antiporter, many types of cancer cells including breast cancer cells are able to readily uptake selenium compared to nontransformed cells. This drives increased antioxidant selenoprotein production, affording cancer cells increased protection against reactive oxygen species and ferroptotic insults. At the same time, this introduces a liability in cancer cells as they must detoxify selenide, a highly toxic selenium intermediate that is formed in the process of selenocysteine metabolism, via the enzyme SEPHS2. We believe this explains why selenium can be both a required nutrient but a toxin at higher doses, and provides a method to selectively poison these cancer cells from the inside out with toxic selenide that they themselves have produced. We continue to examine the implications of increased selenocysteine biosynthesis in cancer cells, and how to utilize this for cancer therapy and even diseases outside of cancer.