Regulation of MDA-MB-231 cell proliferation by GSK-3β involves epigenetic modifications under high glucose conditions

Gupta, Chanchal; Kaur, Jasmine; Tikoo, Kulbhushan

doi:10.1016/j.yexcr.2014.03.019

Cited by 29 publications

(21 citation statements)

References 56 publications

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“…Evidence is particularly strong that GSK3 contributes to the regulation of histone modifications that play a central role in epigenetics. GSK3 can directly phosphorylate histone 1.5 (Happel et al, 2009) and promotes histone 3 phosphorylation, although the mechanism was not identified (Gupta et al, 2014). GSK3 also phosphorylates several histone deacetylases (HDACs).…”

Section: Regulation Of Gsk3-mediated Substrate Phosphorylationmentioning

confidence: 99%

Glycogen synthase kinase-3 (GSK3): Regulation, actions, and diseases

Beurel

Grieco

Jope

2015

Pharmacology & Therapeutics

1,390

1,178

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Glycogen synthase kinase-3 (GSK3) may be the busiest kinase in most cells, with over 100 known substrates to deal with. How does GSK3 maintain control to selectively phosphorylate each substrate, and why was it evolutionarily favorable for GSK3 to assume such a large responsibility? GSK3 must be particularly adaptable for incorporating new substrates into its repertoire, and we discuss the distinct properties of GSK3 that may contribute to its capacity to fulfill its roles in multiple signaling pathways. The mechanisms regulating GSK3 (predominantly post-translational modifications, substrate priming, cellular trafficking, protein complexes) have been reviewed previously, so here we focus on newly identified complexities in these mechanisms, how each of these regulatory mechanism contributes to the ability of GSK3 to select which substrates to phosphorylate, and how these mechanisms may have contributed to its adaptability as new substrates evolved. The current understanding of the mechanisms regulating GSK3 is reviewed, as are emerging topics in the actions of GSK3, particularly its interactions with receptors and receptor-coupled signal transduction events, and differential actions and regulation of the two GSK3 isoforms, GSK3α and GSK3β. Another remarkable characteristic of GSK3 is its involvement in many prevalent disorders, including psychiatric and neurological diseases, inflammatory diseases, cancer, and others. We address the feasibility of targeting GSK3 therapeutically, and provide an update of its involvement in the etiology and treatment of several disorders.

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Section: Regulation Of Gsk3-mediated Substrate Phosphorylationmentioning

confidence: 99%

Glycogen synthase kinase-3 (GSK3): Regulation, actions, and diseases

Beurel

Grieco

Jope

2015

Pharmacology & Therapeutics

1,390

1,178

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“…Together with Snail, GSK-3β functions as a molecular switch for a number of signaling pathways that facilitate EMT. GSK-3β was initially identified as a key protein kinase involved in glycogen metabolism but is now known to modulate various biological events, including cellular proliferation, 14 differentiation, 15 migration, 16 glucose regulation 17 and apoptosis. 18 GSK-3β is highly activated in carcinomas and is known to inhibit tumor migration and invasion and to maintain the epithelial morphology of tumor cells, as GSK-3β inhibition led to the acquisition of the mesenchymal phenotype.…”

Section: Introductionmentioning

confidence: 99%

MCP-1-induced ERK/GSK-3β/Snail signaling facilitates the epithelial–mesenchymal transition and promotes the migration of MCF-7 human breast carcinoma cells

Lü

Chen

et al. 2016

Cell Mol Immunol

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Monocyte chemoattractant protein-1 (MCP-1) is a chemotactic cytokine that can bind to its receptor cysteine-cysteine chemokine receptor 2 (CCR2) and plays an important role in breast cancer cell metastasis. However, the molecular mechanisms underlying MCP-1-induced alterations in cellular functions during tumor progression are poorly understood. Here, we showed that MCP-1 stimulated the epithelial-mesenchymal transition (EMT) and induced the tumorigenesis of breast cancer cells by downregulating E-cadherin, upregulating vimentin and fibronectin, activating matrix metallopeptidase-2 (MMP-2), and promoting migration and invasion. Moreover, MCP-1 treatment reduced glycogen synthase kinase-3β (GSK-3β) activity via the MEK/ERK-mediated phosphorylation of serine-9 in MCF-7 cells. The inhibition of MEK/ERK by U0126 attenuated the MCP-1-induced phosphorylation of GSK-3β and decreased the expression of Snail, an EMT-related transcription factor, leading to the inhibition of MCF-7 cell migration and invasion. Inactivation of GSK-3β by LiCl (lithium chloride) treatment notably increased MMP-2 activity, vascular endothelial growth factor expression and EMT of MCF-7 cells. These findings revealed that MCP-1-induced EMT and migration are mediated by the ERK/GSK-3β/Snail pathway, and identified a potential novel target for therapeutic intervention in breast cancer. Cellular & Molecular Immunology

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“…In a recent study, methylation of cytosine within the promoter region of dystrophin was examined by using Duchenne muscular dystrophy (DMD) knockout mice, and this deficiency was shown to increase MMP-2 expression levels (150). In breast cancer cells MD-MB-231, high glucose led to the phosphorylation of histone 3 at the Ser10 residue while dephosphorylating the Ser9 residue (151). This event correlated with the increase in DNMT1 expression (151).…”

Section: Regulation Of Mmps In Vascular Diseasesmentioning

confidence: 99%

“…In breast cancer cells MD-MB-231, high glucose led to the phosphorylation of histone 3 at the Ser10 residue while dephosphorylating the Ser9 residue (151). This event correlated with the increase in DNMT1 expression (151). Silencing GSK-3β by siRNA inhibited the phosphorylation of H3, and thus decreasing DNMT1 expression (151).…”

Section: Regulation Of Mmps In Vascular Diseasesmentioning

confidence: 99%

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Regulation and involvement of matrix metalloproteinases in vascular diseases

et al. 2016

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Matrix metalloproteinases (MMPs) are a family of zinc dependent endopeptidases whose main function is to degrade and deposit structural proteins within the extracellular matrix (ECM). A dysregulation of MMPs is linked to vascular diseases. MMPs are classified into collagenases, gelatinases, membrane-type, metalloelastase, stromelysins, matrilysins, enamelysins, and unclassified subgroups. The production of MMPs is stimulated by factors such as oxidative stress, growth factors and inflammation which lead to its up- or down-regulation with subsequent ECM remodeling. Normally, excess activation of MMPs is controlled by their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs). An imbalance of MMPs and TIMPs has been implicated in hypertension, atherosclerotic plaque formation and instability, aortic aneurysms and varicose vein wall remodeling. Also, recent evidence suggests epigenetic regulation of some MMPs in angiogenesis and atherosclerosis. Over the years, pharmacological inhibitors of MMPs have been used to modify or prevent the development of the disease with some success. In this review, we discuss recent advances in MMP biology, and their involvement in the manifestation of vascular disease.

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Regulation of MDA-MB-231 cell proliferation by GSK-3β involves epigenetic modifications under high glucose conditions

Cited by 29 publications

References 56 publications

Glycogen synthase kinase-3 (GSK3): Regulation, actions, and diseases

Glycogen synthase kinase-3 (GSK3): Regulation, actions, and diseases

MCP-1-induced ERK/GSK-3β/Snail signaling facilitates the epithelial–mesenchymal transition and promotes the migration of MCF-7 human breast carcinoma cells

Regulation and involvement of matrix metalloproteinases in vascular diseases

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