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Autocrine control of glioma cells adhesion and migration through IRE1α-mediated cleavage of SPARC mRNA
Nicolas Dejeans, Olivier Pluquet, Stéphanie Lhomond, Florence Grise, Marion Bouchecareilh, Amélie Juin, Maud Meynard-Cadars, Aurélien Bidaud-Meynard, Catherine Gentil, Violaine Moreau, Frédéric Saltel, Eric Chevet


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.


  • * Present address: Institut de Biologie de Lille, CNRS UMR8161/Universités Lille 1 et Lille 2/Institut Pasteur de Lille, 1, rue du Pr. Calmette, BP 447, 59021 Lille, France

  • Funding

    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.

  • Supplementary material available online at

  • Accepted May 28, 2012.
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