Effects of mutations in Wnt/β-catenin, hedgehog, Notch and PI3K pathways on GSK-3 activity-Diverse effects on cell growth, metabolism and cancer

被引：128

作者：

McCubrey, James A. ^{[1
]}

Rakus, Dariusz ^{[2
]}

Gizak, Agnieszka ^{[2
]}

Steelman, Linda S. ^{[1
]}

Abrams, Steve L. ^{[1
]}

Lertpiriyapong, Kvin ^{[3
]}

Fitzgerald, Timothy L. ^{[4
]}

Yang, Li V. ^{[5
]}

Montalto, Giuseppe ^{[6
,7
]}

Cervello, Melchiorre ^{[7
]}

Libra, Massimo ^{[8
]}

Nicoletti, Ferdinando ^{[8
]}

Scalisi, Aurora ^{[9
]}

Torino, Francesco ^{[10
]}

Fenga, Concettina ^{[11
]}

Neri, Luca M. ^{[12
]}

Marmiroli, Sandra ^{[13
]}

Cocco, Lucio ^{[14
]}

Martelli, Alberto M. ^{[14
]}

机构：

[1] East Carolina Univ, Brody Sch Med, Dept Microbiol & Immunol, Greenville, NC 27858 USA

[2] Univ Wroclaw, Inst Expt Biol, Dept Anim Mol Physiol, Wroclaw, Poland

[3] East Carolina Univ, Brody Sch Med, Dept Comparat Med, Greenville, NC 27858 USA

[4] East Carolina Univ, Brody Sch Med, Dept Surg, Greenville, NC 27858 USA

[5] East Carolina Univ, Brody Sch Med, Hematol Oncol Sect, Dept Internal Med, Greenville, NC 27858 USA

[6] Univ Palermo, Biomed Dept Internal Med & Specialties, Palermo, Italy

[7] CNR, Ist Biomed & Immunol Mol Alberto Monroy, Palermo, Italy

[8] Univ Catania, Dept Biomed Sci, Catania, Italy

[9] ASP Catania, Unit Oncol Dis, I-95100 Catania, Italy

[10] Univ Roma Tor Vergata, Dept Syst Med, Chair Med Oncol, Rome, Italy

[11] Univ Messina, Policlin G Martino, Occupat Med Sect, Dept Biomed Odontoiatrt Morphol & Funct Images, I-98125 Messina, Italy

[12] Univ Ferrara, Dept Morphol Surg & Expt Med, Ferrara, Italy

[13] Univ Modena & Reggio Emilia, Dept Surg Med Dent & Morphol, Modena, Italy

[14] Univ Bologna, Dipartimento Sci Biomed & Neuromotorie, Bologna, Italy

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2016年 / 1863卷 / 12期

关键词：

GSK-3; Wnt/beta-catenin; PI3K; Akt; mTOR; Hedgehog; Notch; Targeted therapy; Therapy resistance; GLYCOGEN-SYNTHASE KINASE-3; NF-KAPPA-B; WNT SIGNALING PATHWAY; EPITHELIAL-MESENCHYMAL TRANSITION; HEPATOCELLULAR-CARCINOMA CELLS; LUNG ADENOCARCINOMA CELLS; MESSENGER-RNA EXPRESSION; HEREDITARY BREAST-CANCER; EMBRYONIC STEM-CELLS; PANCREATIC-CANCER;

D O I：

10.1016/j.bbamcr.2016.09.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase that participates in an array of critical cellular processes. GSK-3 was first characterized as an enzyme that phosphorylated and inactivated glycogen synthase. However, subsequent studies have revealed that this moon-lighting protein is involved in numerous signaling pathways that regulate not only metabolism but also have roles in: apoptosis, cell cycle progression, cell renewal, differentiation, embiyogenesis, migration, regulation of gene transcription, stem cell biology and survival. In this review, we will discuss the roles that GSK-3 plays in various diseases as well as how this pivotal kinase interacts with multiple signaling pathways such as: PI3K/PTEN/Akt/mTOR, Ras/Raf/MEK/ERK, Wnt/beta-catenin, hedgehog, Notch and TP53. Mutations that occur in these and other pathways can alter the effects that natural GSK-3 activity has on regulating these signaling circuits that can lead to cancer as well as other diseases. The novel roles that microRNAs play in regulation of the effects of GSK-3 will also be evaluated. Targeting GSK-3 and these other pathways may improve therapy and overcome therapeutic resistance. (C) 2016 Elsevier B.V. All rights reserved.

引用

页码：2942 / 2976

页数：35

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