期刊
ONCOTARGET
卷 5, 期 10, 页码 2881-2911出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.2037
关键词
GSK-3; cancer stem cells; Wnt/beta-catenin; PI3K; Akt; mTOR; Hedgehog; Notch; Targeted Therapy; Therapy Resistance; Mutations; Rapamycin
资金
- USAMRMC [BC022276]
- Intramural RECDA Award
- Italian Association for Cancer Research (AIRC)
- Triad Chapter of Golfers Against Cancer
- MIUR-PRIN
- Italian MIUR-FIRB Accordi di Programma
- Italian Ministero dell'Istruzione, dell'Universita e della Ricerca (Ministry for Education, Universities and Research) - FIRB-MERIT [RBNE08YYBM]
- Italian Ministry of Economy and Finance
- Italian Ministry of Health, Ricerca Finalizzata Stemness Molecular Determinants of Stemness and Mesenchymal Phenotype in Breast Cancer
- MIUR FIRB [RBAP11ZJFA_001]
- CRO, the Italian Association for Cancer Research, (AIRC) [MCO10016]
- Italian Ministry of Health, and Regione Friuli Venezia-Giulia
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.
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