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FOXO s support the metabolic requirements of normal and tumor cells by promoting IDH 1 expression
Author(s) -
Charitou Paraskevi,
RodriguezColman Maria,
Gerrits Johan,
Triest Miranda,
Groot Koerkamp Marian,
Hornsveld Marten,
Holstege Frank,
VerhoevenDuif Nanda M,
Burgering Boudewijn MT
Publication year - 2015
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201439096
Subject(s) - microbiology and biotechnology , chemistry , biology
Abstract FOXO transcription factors are considered bona fide tumor suppressors; however, recent studies showed FOXO s are also required for tumor survival. Here, we identify FOXO s as transcriptional activators of IDH 1. FOXO s promote IDH 1 expression and thereby maintain the cytosolic levels of α‐ketoglutarate and NADPH . In cancer cells carrying mutant IDH 1, FOXO s likewise stimulate mutant IDH 1 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 FOXO s in both tumor suppression and promotion.