title: Roles of GSK-3 and microRNAs on epithelial mesenchymal transition and cancer stem cells.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: McCubrey
authors.affiliation: Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, NC, USA.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Fitzgerald
authors.affiliation: Department of Internal Medicine, Hematology/Oncology Section, Brody School of Medicine at East Carolina University, Greenville, NC, USA.
authors.forename: Li V
authors.initials: LV
authors.lastname: Yang
authors.affiliation: Department of Comparative Medicine, Brody School of Medicine at East Carolina University, Greenville, NC, USA.
authors.forename: Kvin
authors.initials: K
authors.lastname: Lertpiriyapong
authors.affiliation: Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Steelman
authors.affiliation: Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Abrams
authors.affiliation: Biomedical Department of Internal Medicine and Specialties, University of Palermo, Palermo, Italy.|Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e Immunologia Molecolare "Alberto Monroy", Palermo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Montalto
authors.affiliation: Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e Immunologia Molecolare "Alberto Monroy", Palermo, Italy.
authors.forename: Melchiorre
authors.initials: M
authors.lastname: Cervello
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Luca M
authors.initials: LM
authors.lastname: Neri
authors.affiliation: Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Cocco
authors.affiliation: Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy.
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Martelli
authors.affiliation: Chair of Medical Biochemistry, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Laidler
authors.affiliation: Chair of Medical Biochemistry, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Dulińska-Litewka
authors.affiliation: Department of Animal Molecular Physiology, Institute of Experimental Biology, Wroclaw University, Wroclaw, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Rakus
authors.affiliation: Department of Animal Molecular Physiology, Institute of Experimental Biology, Wroclaw University, Wroclaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gizak
authors.affiliation: Department of Biomedical and Biotechnological Sciences - Oncological, Clinical and General Pathology Section, University of Catania, Catania, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.affiliation: Department of Biomedical and Biotechnological Sciences - Oncological, Clinical and General Pathology Section, University of Catania, Catania, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Falzone
authors.affiliation: Department of Biomedical and Biotechnological Sciences - Oncological, Clinical and General Pathology Section, University of Catania, Catania, Italy.
authors.forename: Saverio
authors.initials: S
authors.lastname: Candido
authors.affiliation: Department of Biomedical and Biotechnological Sciences - Oncological, Clinical and General Pathology Section, University of Catania, Catania, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Libra
mesh_terms: D000818:Animals; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D035683:MicroRNAs; D038362:Glycogen Synthase Kinase 3
keywords: Akt; GSK-3; PI3K; Wnt/beta-catenin; cancer stem cells