2014
DOI: 10.18632/oncotarget.2037
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GSK-3 as potential target for therapeutic intervention in cancer

Abstract: 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 associa… Show more

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Cited by 419 publications
(392 citation statements)
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References 298 publications
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“…Particularly, the cytoplasmic domain of Ecadherin contains several phosphorylation sites for CKII and GSK3β (131). However, we found an increase of AKTdependent phosphorylation of GSK3β (S9), which is known to completely suppress its kinase activity (132). Therefore, it is unlikely that GSK3β is responsible for the observed effect.…”
Section: Targeting the Nk1r Compromises Canonical Wnt Signaling In Hementioning
confidence: 58%
“…Particularly, the cytoplasmic domain of Ecadherin contains several phosphorylation sites for CKII and GSK3β (131). However, we found an increase of AKTdependent phosphorylation of GSK3β (S9), which is known to completely suppress its kinase activity (132). Therefore, it is unlikely that GSK3β is responsible for the observed effect.…”
Section: Targeting the Nk1r Compromises Canonical Wnt Signaling In Hementioning
confidence: 58%
“…Such a change in the GSK-3β activity seems not to correlate with alterations in the IR protein level in that period (decreased expression) but since we have not measured the IR tyrosine kinase activity, it could not be excluded that it might be increased at this time point to compensate for reduced IR protein level and consequently to lead to such changes in p/t GSK-3β ratio (activity). Additionally, it has to be kept in mind that GSK-3β phosphorylation homeostasis might be affected by different kinases besides IR-PI-3K-Akt/PKB pathway, like ERK which can phosphorylate GSK-3β on T48 site making GSK-3 β inactive, as regulated through IR-MAPK pathway (McCubrey et al 2014). This speculation might be a possible explanation also of the tau hyperphoshorylation (PHF1) we observed in the period of 1-3 months after STZ-icv administration when GSK-3β activity was not increased.…”
Section: Discussionmentioning
confidence: 99%
“…Inhibiting GSK3 activity with small molecules may be considered a double-edged sword as it could stimulate malignant transformation and cancer growth by activating Wnt/␤-Catenin signaling or by stabilizing oncogenes regulated by Wnt/STOP such as c-Jun and c-Myc [6,11]. However, long-term studies in mice treated with GSK3 inhibitors have not revealed oncogenic effects [97]. Additionally, the GSK3 inhibitor Lithium Chloride, which has long been used to treat patients with bipolar disorder, has never been linked to increased cancer incidence [97].…”
Section: Pharmacological Approachesmentioning
confidence: 99%
“…However, long-term studies in mice treated with GSK3 inhibitors have not revealed oncogenic effects [97]. Additionally, the GSK3 inhibitor Lithium Chloride, which has long been used to treat patients with bipolar disorder, has never been linked to increased cancer incidence [97]. In fact, it has been observed that GSK3 inhibitors can decrease cellular proliferation of some cancers, including melanoma, prostate, and pancreatic tumors [98,99].…”
Section: Pharmacological Approachesmentioning
confidence: 99%