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 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.
Original language | English (US) |
---|---|
Pages (from-to) | 2881-2911 |
Number of pages | 31 |
Journal | Oncotarget |
Volume | 5 |
Issue number | 10 |
DOIs | |
State | Published - 2014 |
Keywords
- Akt
- Cancer stem cells
- GSK-3
- Hedgehog
- MTOR
- Mutations
- Notch
- PI3K
- Rapamycin
- Targeted therapy
- Therapy resistance
- Wnt/beta-catenin
ASJC Scopus subject areas
- Oncology