Journal
ONCOTARGET
Volume 8, Issue 8, Pages 14221-14250Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.13991
Keywords
GSK-3; cancer stem cells; Wnt/beta-catenin; PI3K; Akt
Categories
Funding
- East Carolina University Grant [111104]
- Intesa San Paolo Foundation
- MIUR FIRB [RBAP11ZJFA_001]
- Lega Italiana per la Lotta contro i Tumori grant
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Various signaling pathways exert critical roles in the epithelial to mesenchymal transition (EMT) and cancer stem cells (CSCs). The Wnt/beta-catenin, PI3K/PTEN/ Akt/mTORC, Ras/Raf/MEK/ERK, hedgehog (Hh), Notch and TP53 pathways elicit essential regulatory influences on cancer initiation, EMT and progression. A common kinase involved in all these pathways is moon-lighting kinase glycogen synthase kinase-3 (GSK-3). These pathways are also regulated by micro-RNAs (miRs). TP53 and components of these pathways can regulate the expression of miRs. Targeting members of these pathways may improve cancer therapy in those malignancies that display their abnormal regulation. This review will discuss the interactions of the multi-functional GSK-3 enzyme in the Wnt/beta-catenin, PI3K/PTEN/Akt/mTORC, Ras/Raf/MEK/ERK, Hh, Notch and TP53 pathways. The regulation of these pathways by miRs and their effects on CSC generation, EMT, invasion and metastasis will be discussed.
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