Selenium detoxification is required for cancer-cell survival.

Nature Metabolism
Anne E CarlisleDohoon Kim

Abstract

The micronutrient selenium is incorporated via the selenocysteine biosynthesis pathway into the rare amino acid selenocysteine, which is required in selenoproteins such as glutathione peroxidases and thioredoxin reductases1,2. Here, we show that selenophosphate synthetase 2 (SEPHS2), an enzyme in the selenocysteine biosynthesis pathway, is essential for survival of cancer, but not normal, cells. SEPHS2 is required in cancer cells to detoxify selenide, an intermediate that is formed during selenocysteine biosynthesis. Breast and other cancer cells are selenophilic, owing to a secondary function of the cystine/glutamate antiporter SLC7A11 that promotes selenium uptake and selenocysteine biosynthesis, which, by allowing production of selenoproteins such as GPX4, protects cells against ferroptosis. However, this activity also becomes a liability for cancer cells because selenide is poisonous and must be processed by SEPHS2. Accordingly, we find that SEPHS2 protein levels are elevated in samples from people with breast cancer, and that loss of SEPHS2 impairs growth of orthotopic mammary-tumour xenografts in mice. Collectively, our results identify a vulnerability of cancer cells and define the role of selenium metabolism in cancer.

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Citations

Jul 28, 2020·Oncogene·Namgyu LeeDohoon Kim
Jul 23, 2020·Nature Metabolism·Anastasia KaparaBarrie Peck
Dec 22, 2020·Journal of Cellular and Molecular Medicine·Yefei RongWenhui Lou
Jan 28, 2021·Biology·Min Ji KimSung Eun Kim
Jan 14, 2021·International Journal of Molecular Sciences·Lucia A SealeMarla J Berry
Mar 2, 2021·Redox Biology·Kristina LossowAnna P Kipp
Apr 10, 2021·Comprehensive Reviews in Food Science and Food Safety·Minhao XieYong Fang
Apr 20, 2021·Frontiers in Molecular Biosciences·Xiwen WuBaogang Peng
Jun 15, 2021·Frontiers in Neuroscience·Eduard YakubovHans-Herbert Steiner
Aug 16, 2021·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Ali RazaghiMikael Björnstedt
Sep 2, 2021·Biological Trace Element Research·Ruili ZhangXiaodan Huang

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Methods Mentioned

BETA
xenograft
Assay
xenografts
electrophoresis
FACS

Software Mentioned

R
ImageJ

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