Selenium detoxification is required for cancer-cell survival

Area of Science:

• Biochemistry
• Cancer Biology
• Metabolic Pathways

Background:

• Selenium is a micronutrient incorporated into selenocysteine, essential for selenoproteins like glutathione peroxidases.
• Selenocysteine biosynthesis involves intermediates, including potentially toxic selenide.

Purpose of the Study:

• To investigate the role of selenophosphate synthetase 2 (SEPHS2) in cancer cell survival.
• To identify vulnerabilities in cancer cell metabolism related to selenium.
• To explore SEPHS2 as a potential therapeutic target.

Main Methods:

• Analysis of SEPHS2 function in cancer versus normal cells.
• Investigating the role of SEPHS2 in detoxifying selenide during selenocysteine biosynthesis.
• Examining SEPHS2 protein levels in human breast cancer samples.
• Assessing the impact of SEPHS2 loss on tumor growth in orthotopic xenograft models.

Main Results:

• SEPHS2 is essential for the survival of cancer cells, but not normal cells.
• Cancer cells, particularly breast cancer cells, exhibit increased selenium uptake and selenocysteine biosynthesis, leading to selenide accumulation.
• Elevated SEPHS2 protein levels were observed in breast cancer samples.
• Loss of SEPHS2 function significantly impaired the growth of mammary tumors in mice.

Conclusions:

• SEPHS2 plays a critical role in detoxifying selenide, a toxic intermediate, making it essential for cancer cell survival.
• Cancer cells' reliance on selenium metabolism creates a vulnerability that can be targeted by inhibiting SEPHS2.
• Targeting SEPHS2 represents a novel therapeutic strategy for treating cancers, especially breast cancer.