Department of Cancer and Cell Biology, University of Cincinnati, Cincinnati, OH 45267, USA.
Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2361-5. doi: 10.1073/pnas.1013629108. Epub 2011 Jan 24.
Pten inactivation promotes cell survival in leukemia cells by activating glycolytic metabolism. We found that targeting ribosomal protein S6 kinase 1 (S6K1) in Pten-deficient cells suppressed glycolysis and induced apoptosis. S6K1 knockdown decreased expression of HIF-1α, and HIF-1α was sufficient to restore glycolysis and survival of cells lacking S6K1. In the Pten(fl/fl) Mx1-Cre(+) mouse model of leukemia, S6K1 deletion delayed the development of leukemia. Thus, S6K1 is a critical mediator of glycolytic metabolism, cell survival, and leukemogenesis in Pten-deficient cells.
Pten 失活通过激活糖酵解代谢促进白血病细胞的存活。我们发现，靶向 Pten 缺陷细胞中的核糖体蛋白 S6 激酶 1（S6K1）可抑制糖酵解并诱导细胞凋亡。S6K1 敲低降低了 HIF-1α 的表达，并且 HIF-1α 足以恢复缺乏 S6K1 的细胞的糖酵解和存活。在 Pten(fl/fl)Mx1-Cre(+)小鼠白血病模型中，S6K1 缺失延迟了白血病的发展。因此，S6K1 是 Pten 缺陷细胞中糖酵解代谢、细胞存活和白血病发生的关键介质。
