Silencing of the MT1-MMP/ G6PT axis suppresses calcium mobilization by sphingosine-1-phosphate in glioblastoma cells.
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.
Fortier
Simon
S
Laboratoire d'Oncologie Moléculaire, Département de Chimie, Centre BioMed, Université du Québec à Montréal, Succ Centre-ville, Montreal, Quebec, Canada.
Labelle
Dominique
D
Sina
Asmaa
A
Moreau
Robert
R
Annabi
Borhane
B
D017920:Antiporters / Q000235:genetics*; D020013:Calcium Signaling / Q000187:drug effects*; D002633:Chemotaxis / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020868:Gene Silencing / Q000187:drug effects; D005909:Glioblastoma / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D053511:Matrix Metalloproteinase 14 / Q000235:genetics*; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D017920:Antiporters; D008246:Lysophospholipids; D009004:Monosaccharide Transport Proteins; C503531:SLC37A4 protein, human; C060506:sphingosine 1-phosphate; D048049:Extracellular Signal-Regulated MAP Kinases; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14; D013110:Sphingosine