Multifaceted roles of GSK-3 and Wnt/β-catenin in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

S L Abrams (Creator)

J Basecke (Creator)

F E Bertrand (Creator)

M Cervello (Creator)

L Cocco (Creator)

A B D'Assoro (Creator)

N M Davis (Creator)

M Libra (Creator)

R Maestro (Creator)

A M Martelli (Creator)

J A McCubrey (Creator)

G Montalto (Creator)

F Nicoletti (Creator)

L S Steelman (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Extracted text; Glycogen synthase kinase-3 (GSK-3) is well documented to participate in a complex array of critical cellular processes. It was initially identified in rat skeletal muscle as a serine/threonine kinase that phosphorylated and inactivated glycogen synthase. This versatile protein is involved in numerous signaling pathways that influence metabolism, embryogenesis, differentiation, migration, cell cycle progression and survival. Recently, GSK-3 has been implicated in leukemia stem cell pathophysiology and may be an appropriate target for its eradication. In this review, we will discuss the roles that GSK-3 plays in hematopoiesis and leukemogenesis as how this pivotal kinase can interact with multiple signaling pathways such as: Wnt/ß-catenin, phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt/mammalian target of rapamycin (mTOR), Ras/Raf/MEK/extracellular signal-regulated kinase (ERK), Notch and others. Moreover, we will discuss how targeting GSK-3 and these other pathways can improve leukemia therapy and may overcome therapeutic resistance. In summary, GSK-3 is a crucial regulatory kinase interacting with multiple pathways to control various physiological processes, as well as leukemia stem cells, leukemia progression and therapeutic resistance. GSK-3 and Wnt are clearly intriguing therapeutic targets.

Additional Information

Publication

Other

Leukemia; 28:1 p. 15-33

Language: English

Date: 2014

Keywords

Akt, GSK-3, therapy resistance, Wnt/ß-catenin, leukemia stem cells, targeted therapy

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