AI Article Synopsis
- FOXO transcription factors are known as tumor suppressors, but they also play a crucial role in tumor survival by activating certain genes.
- FOXOs enhance the expression of IDH1, which helps maintain important cellular substances like α-ketoglutarate and NADPH.
- In cancer cells with mutant IDH1, FOXOs still boost IDH1 expression, supporting the production of 2-hydroxyglutarate, a compound that promotes cancer growth and inhibits important enzymes involved in DNA regulation.
Article Abstract
FOXO transcription factors are considered bona fide tumor suppressors; however, recent studies showed FOXOs are also required for tumor survival. Here, we identify FOXOs as transcriptional activators of IDH1. FOXOs promote IDH1 expression and thereby maintain the cytosolic levels of α-ketoglutarate and NADPH. In cancer cells carrying mutant IDH1, FOXOs likewise stimulate mutant IDH1 expression and maintain the levels of the oncometabolite 2-hydroxyglutarate, which stimulates cancer cell proliferation and inhibits TET enzymes and histone demethylases. Combined, our data provide a new paradigm for the paradoxical role of FOXOs in both tumor suppression and promotion.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388612 | PMC |
| http://dx.doi.org/10.15252/embr.201439096 | DOI Listing |
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