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

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

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 t...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2011-02, Vol.108 (6), p.2361-2365
Hauptverfasser: Tandon, Preeti, Gallo, Catherine A, Khatri, Shikha, Barger, Jennifer F, Yepiskoposyan, Hasmik, Plas, David R
Format: Artikel
Sprache:eng
Schlagworte:
Animal models
Animals
Apoptosis
Biological Sciences
Bone marrow cells
Cancer
Cell growth
Cell Line, Tumor
Cell lines
Cells
Cellular metabolism
Cultured cells
Disease Models, Animal
Gene expression
Gene expression regulation
Gene Knockdown Techniques
Glycolysis
Hypoxia-Inducible Factor 1, alpha Subunit - genetics
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Kinases
Leukemia
Leukemia - enzymology
Leukemia - genetics
Metabolism
Mice
Mice, Knockout
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
PTEN Phosphohydrolase - genetics
PTEN Phosphohydrolase - metabolism
Ribosomal Protein S6 Kinases, 90-kDa - genetics
Ribosomal Protein S6 Kinases, 90-kDa - metabolism
Rodents
Survival analysis
Viability
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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 Ptenfl/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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1013629108