Silencing of the MT1-MMP/ G6PT axis suppresses calcium mobilization by sphingosine-1-phosphate in glioblastoma cells |
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Authors: | Fortier Simon Labelle Dominique Sina Asmaa Moreau Robert Annabi Borhane |
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Institution: | Laboratoire d'Oncologie Moléculaire, Département de Chimie, Centre BioMed, Université du Québec à Montréal, Succ Centre-ville, Montreal, Quebec, Canada. |
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Abstract: | The contributions of membrane type-1 matrix metalloproteinase (MT1-MMP) and of the glucose-6-phosphate transporter (G6PT) in sphingosine-1-phosphate (S1P)-mediated Ca(2+) mobilization were assessed in glioblastoma cells. We show that gene silencing of MT1-MMP or G6PT decreased the extent of S1P-induced Ca(2+) mobilization, chemotaxis, and extracellular signal-related kinase phosphorylation. Chlorogenic acid and (-)-epigallocatechin-3-gallate, two diet-derived inhibitors of G6PT and of MT1-MMP, respectively, reduced S1P-mediated Ca(2+) mobilization. An intact MT1-MMP/G6PT signaling axis is thus required for efficient Ca(2+) mobilization in response to bioactive lipids such as S1P. Targeted inhibition of either MT1-MMP or G6PT may lead to reduced infiltrative and invasive properties of brain tumor cells. |
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Keywords: | CHL chlorogenic acid ECM extracellular matrix EGCg (−)-epigallocatechin-3-gallate ER endoplasmic reticulum ERK extracellular signal-related kinase 1/2 bFGF basic fibroblast growth factor G6PT glucose-6-phosphate transporter MMP matrix metalloproteinase MT1-MMP membrane type-1 MMP S1P sphingosine-1-phosphate S1PR S1P receptor SphK sphingosine kinase |
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