Requirement for ribosomal protein S6 kinase 1 to mediate glycolysis and apoptosis resistance induced by Pten deficiency

被引：61

作者：

Tandon, Preeti ^{[1
]}

Gallo, Catherine A. ^{[1
]}

Khatri, Shikha ^{[1
]}

Barger, Jennifer F. ^{[1
]}

Yepiskoposyan, Hasmik ^{[1
]}

Plas, David R. ^{[1
]}

机构：

[1] Univ Cincinnati, Dept Canc & Cell Biol, Cincinnati, OH 45267 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 06期

基金：

美国国家卫生研究院;

关键词：

BCL-X-L; PANCREATIC-ISLETS; INSULIN-RELEASE; AKT ACTIVATION; CELL-GROWTH; STEM-CELLS; SURVIVAL; CANCER; TRANSLATION; EXPRESSION;

D O I：

10.1073/pnas.1013629108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-1 alpha, and HIF-1 alpha 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.

引用

页码：2361 / 2365

页数：5

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