Abstract LB-256: S6K1 mediates glycolysis and apoptosis resistance in Pten deficient cells

• Published in: Cancer research (Chicago, Ill.) Ill.), 2011-04, Vol.71 (8_Supplement), p.LB-256-LB-256
• Main Authors: Tandon, Preeti, Gallo, Catherine A., Khatri, Shikha, Plas, David R.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2011-LB-256

Pten loss and subsequent Akt activation promotes cell survival in human cancer cells through activation of glycolytic metabolism and repression of pro-apoptotic factors. Because sustained glycolysis is required for Akt dependent apoptosis resistance, we investigated the downstream signaling components that mediate Akt dependent increases in glycolysis in Pten-deficient cells. Loss of the ribosomal protein S6K1 in Pten-deficient cells prevented Akt-induced glycolysis and triggered Bax translocation and commitment to apoptosis. Inactivation of S6K1 was associated with decreased expression of the pro-glycolytic HIF1α transcription factor. Restoring HIF1α expression was sufficient to restore both glycolysis and cell survival in S6K1-deficient cells. Conversely, inhibiting HIF1α expression in Pten deficient cells resulted in decreased glycolysis and cell survival, mimicking the loss of S6K1. In vivo, S6K1 deficiency delayed the development of lethal disease in the Pten fl/fl Mx-1 Cre+ model of leukemia. Thus, together the data suggest that S6K1 is a useful target for counteracting the metabolic program that supports apoptosis resistance in Pten-deficient cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-256. doi:10.1158/1538-7445.AM2011-LB-256