TY - JOUR
T1 - GSK-3 as potential target for therapeutic irvention in cancer
AU - Mccubrey, James A.
AU - Steelman, Linda S.
AU - Bertrand, Fred E.
AU - Davis, Nicole M.
AU - Sokolosky, Melissa
AU - Abrams, Steve L.
AU - Montalto, Giuseppe
AU - D'Assoro, Antonino B.
AU - Libra, Massimo
AU - Nicoletti, Ferdinando
AU - Maestro, Roberta
AU - Basecke, Jorg
AU - Rakus, Dariusz
AU - Gizak, Agnieszka
AU - Demidenko, Zoya
AU - Cocco, Lucio
AU - Martelli, Alberto M.
AU - Cervello, Melchiorre
PY - 2014
Y1 - 2014
N2 - The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially identified and studied in the regulation of glycogen synthesis. GSK-3 functions in a wide range of cellular processes. Aberrant activity of GSK-3 has been implicated in many human pathologies including: bipolar depression, Alzheimer's disease, Parkinson's disease, cancer, non-insulin-dependent diabetes mellitus (NIDDM) and others. In some cases, suppression of GSK-3 activity by phosphorylation by Akt and other kinases has been associated with cancer progression. In these cases, GSK-3 has tumor suppressor functions. In other cases, GSK-3 has been associated with tumor progression by stabilizing components of the beta-catenin complex. In these situations, GSK-3 has oncogenic properties. While many inhibitors to GSK-3 have been developed, their use remains controversial because of the ambiguous role of GSK-3 in cancer development. In this review, we will focus on the diverse roles that GSK-3 plays in various human cancers, in particular in solid tumors. Recently, GSK-3 has also been implicated in the generation of cancer stem cells in various cell types. We will also discuss how this pivotal kinase interacts with multiple signaling pathways such as: PI3K/PTEN/Akt/mTORC1, Ras/Raf/MEK/ERK, Wnt/beta-catenin, Hedgehog, Notch and others.
AB - The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially identified and studied in the regulation of glycogen synthesis. GSK-3 functions in a wide range of cellular processes. Aberrant activity of GSK-3 has been implicated in many human pathologies including: bipolar depression, Alzheimer's disease, Parkinson's disease, cancer, non-insulin-dependent diabetes mellitus (NIDDM) and others. In some cases, suppression of GSK-3 activity by phosphorylation by Akt and other kinases has been associated with cancer progression. In these cases, GSK-3 has tumor suppressor functions. In other cases, GSK-3 has been associated with tumor progression by stabilizing components of the beta-catenin complex. In these situations, GSK-3 has oncogenic properties. While many inhibitors to GSK-3 have been developed, their use remains controversial because of the ambiguous role of GSK-3 in cancer development. In this review, we will focus on the diverse roles that GSK-3 plays in various human cancers, in particular in solid tumors. Recently, GSK-3 has also been implicated in the generation of cancer stem cells in various cell types. We will also discuss how this pivotal kinase interacts with multiple signaling pathways such as: PI3K/PTEN/Akt/mTORC1, Ras/Raf/MEK/ERK, Wnt/beta-catenin, Hedgehog, Notch and others.
KW - Akt
KW - Cancer stem cells
KW - GSK-3
KW - Hedgehog
KW - MTOR
KW - Mutations
KW - Notch
KW - PI3K
KW - Rapamycin
KW - Targeted therapy
KW - Therapy resistance
KW - Wnt/beta-catenin
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U2 - 10.18632/oncotarget.2037
DO - 10.18632/oncotarget.2037
M3 - Article
C2 - 24931005
AN - SCOPUS:84902094632
VL - 5
SP - 2881
EP - 2911
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 10
ER -