Autocrine control of glioma cells adhesion and migration through IRE1α-mediated cleavage of SPARC mRNA

Autor: 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.
Přispěvatelé: Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine Purpan, This work was supported by the Avenir program of Institut National de la Santé et de la Recherche Médicale, Institut national du cancer, Ligue Contre le Cancer to E.C., the French Association pour la Recherche contre le Cancer to O.P., La Ligue contre le Cancer to N.D., and the Cancéropôle Grand Sud-Ouest to C.G., We thank the Chevet lab for critical reading of the manuscript. We are indebted to Sebastien Marais (Bordeaux Imaging Center, Bordeaux, France) for help with the ImageJ program.
Rok vydání: 2012
Předmět:
cell migration
[SDV]Life Sciences [q-bio]
MESH: Cell Movement*/genetics
MESH: Glioma/genetics
MESH: Brain Neoplasms/pathology
Cell Movement
MESH: Extracellular Matrix Proteins/metabolism
MESH: Actin Cytoskeleton/metabolism
Tumor Cells
Cultured
Osteonectin
MESH: Signal Transduction/genetics
MESH: Autocrine Communication*/genetics
Extracellular Matrix Proteins
Brain Neoplasms
MESH: Gene Expression Regulation
Neoplastic
Glioma
MESH: RNA
Messenger/metabolism
Gene Expression Regulation
Neoplastic
Actin Cytoskeleton
Autocrine Communication
MESH: Endoribonucleases/metabolism
MESH: Glioma/pathology
MESH: RNA
Messenger/genetics
Signal Transduction
Down-Regulation
[SDV.CAN]Life Sciences [q-bio]/Cancer
IRE1
Protein Serine-Threonine Kinases
MESH: Spheroids
Cellular/pathology
Models
Biological
MESH: Down-Regulation/genetics
MESH: Gene Expression Profiling
MESH: Cell Proliferation
Spheroids
Cellular
Endoribonucleases
Cell Adhesion
MESH: Osteonectin/genetics
MESH: Protein-Serine-Threonine Kinases/metabolism
Humans
MESH: Tumor Cells
Cultured
RNA
Messenger
MESH: Osteonectin/metabolism
MESH: rhoA GTP-Binding Protein/metabolism
Cell Proliferation
MESH: Extracellular Matrix Proteins/genetics
MESH: Humans
Gene Expression Profiling
MESH: Models
Biological
SPARC
MESH: Cell Adhesion/genetics
MESH: Brain Neoplasms/genetics
rhoA GTP-Binding Protein
Endoplasmic reticulum
Zdroj: Journal of Cell Science
Journal of Cell Science, Company of Biologists, 2012, 125 (18), pp.4278-4287. ⟨10.1242/jcs.099291⟩
ISSN: 1477-9137
0021-9533
DOI: 10.1242/jcs.099291⟩
Popis: International audience; 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.
Databáze: OpenAIRE
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