Autocrine control of glioma cells adhesion and migration through IRE1 -mediated cleavage of SPARC mRNA

The endoplasmic reticulum (ER) is an organelle specialized for the folding and assembly of secretory and transmembrane proteins. ER homeostasis is often perturbed in tumor cells because of dramatic changes in the microenvironment of solid tumors, thereby leading to the activation of an adaptive mech...

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Veröffentlicht in:Journal of cell science 2012-11, Vol.125 (18), p.4278-4287
Hauptverfasser: Dejeans, N., Pluquet, O., Lhomond, S., Grise, F., Bouchecareilh, M., Juin, A., Meynard-Cadars, M., Bidaud-Meynard, A., Gentil, C., Moreau, V., Saltel, F., Chevet, E.
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container_end_page 4287
container_issue 18
container_start_page 4278
container_title Journal of cell science
container_volume 125
creator Dejeans, N.
Pluquet, O.
Lhomond, S.
Grise, F.
Bouchecareilh, M.
Juin, A.
Meynard-Cadars, M.
Bidaud-Meynard, A.
Gentil, C.
Moreau, V.
Saltel, F.
Chevet, E.
description The endoplasmic reticulum (ER) is an organelle specialized for the folding and assembly of secretory and transmembrane proteins. ER homeostasis is often perturbed in tumor cells because of dramatic changes in the microenvironment of solid tumors, thereby leading to the activation of an adaptive mechanism named the unfolded protein response (UPR). The activation of the UPR sensor IRE1α has been described to play an important role in tumor progression. However, the molecular events associated with this phenotype remain poorly characterized. In the present study, we examined the effects of IRE1α signaling on the adaptation of glioma cells to their microenvironment. We show that the characteristics of U87 cell migration are modified under conditions where IRE1α activity is impaired (DN_IRE1). This is linked to increased stress fiber formation and enhanced RhoA activity. Gene expression profiling also revealed that loss of functional IRE1α signaling mostly resulted in the upregulation of genes encoding extracellular matrix proteins. Among these genes, Sparc, whose mRNA is a direct target of IRE1α endoribonuclease activity, was in part responsible for the phenotypic changes associated with IRE1α inactivation. Hence, our data demonstrate that IRE1α is a key regulator of SPARC expression in vitro in a glioma model. Our results also further support the crucial contribution of IRE1α to tumor growth, infiltration and invasion and extend the paradigm of secretome control in tumor microenvironment conditioning.
doi_str_mv 10.1242/jcs.099291
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source EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; Company of Biologists
subjects Actin Cytoskeleton/metabolism
Autocrine Communication/genetics
Brain Neoplasms/genetics
Brain Neoplasms/pathology
Cancer
Cell Adhesion/genetics
Cell Movement/genetics
Cell Proliferation
Down-Regulation/genetics
Endoribonucleases/metabolism
Extracellular Matrix Proteins/genetics
Extracellular Matrix Proteins/metabolism
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Glioma/genetics
Glioma/pathology
Humans
Life Sciences
Models, Biological
Osteonectin/genetics
Osteonectin/metabolism
Protein-Serine-Threonine Kinases/metabolism
rhoA GTP-Binding Protein/metabolism
RNA, Messenger/genetics
RNA, Messenger/metabolism
Signal Transduction/genetics
Spheroids, Cellular/pathology
Tumor Cells, Cultured
title Autocrine control of glioma cells adhesion and migration through IRE1 -mediated cleavage of SPARC mRNA
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