| First Author | Khatri S | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 21 | Pages | 15960-5 |
| PubMed ID | 20371605 | Mgi Jnum | J:163882 |
| Mgi Id | MGI:4830071 | Doi | 10.1074/jbc.M110.121871 |
| Citation | Khatri S, et al. (2010) FOXO3a regulates glycolysis via transcriptional control of tumor suppressor TSC1. J Biol Chem 285(21):15960-5 |
| abstractText | Akt signal transduction induces coordinated increases in glycolysis and apoptosis resistance in a broad spectrum of cancers. Downstream of Akt, the FoxO transcription factors regulate apoptosis via Bim, but the contributions of FoxOs in regulating Akt-induced glycolysis are not well described. We find that FoxO3a knockdown is sufficient to induce apoptosis resistance in conjunction with elevated glycolysis. Glycolysis in FoxO3a-deficient cells was associated with increased S6K1 phosphorylation and was sensitive to rapamycin, an inhibitor of the mTORC1 pathway that has been linked to glycolysis regulation. We show that mTORC1-dependent glycolysis is increased in FoxO3a knockdown cells due to decreased expression of the TSC1 tumor suppressor that opposes mTORC1 activation. FoxO3a binds to and transactivates the TSC1 promoter, indicating a key role for FoxO3a in regulating TSC1 expression. Together, these data demonstrate that FoxO3a regulates glycolysis downstream of Akt through transcriptional control of Tsc1. |
