The chemotherapeutic agent bortezomib induces the formation of stress granulesReportar como inadecuado




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Cancer Cell International

, 10:12

First Online: 29 April 2010Received: 09 March 2010Accepted: 29 April 2010

Abstract

BackgroundCytoplasmic stress granules SGs are specialized storage sites of untranslated mRNAs whose formation occurs under different stress conditions and is often associated with cell survival. SGs-inducing stresses include radiations, hypoxia, viral infections, and chemical inhibitors of specific translation initiation factors. The FDA-approved drug bortezomib Velcade is a peptide boronate inhibitor of the 26S proteasome that is very efficient for the treatment of myelomas and other hematological tumors. Solid tumors are largely refractory to bortezomib. In the present study, we investigated the formation of SGs following bortezomib treatment.

ResultsWe show that bortezomib efficiently induces the formation of SGs in cancer cells. This process involves the phosphorylation of translation initiation factor eIF2α by heme-regulated inhibitor kinase HRI. Depletion of HRI prevents bortezomib-induced formation of SGs and promotes apoptosis.

ConclusionsThis is the first study describing the formation of SGs by a chemotherapeutic compound. We speculate that the activation of HRI and the formation of SGs might constitute a mechanism by which cancer cells resist bortezomib-mediated apoptosis.

Electronic supplementary materialThe online version of this article doi:10.1186-1475-2867-10-12 contains supplementary material, which is available to authorized users.

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Autor: Marie-Josée Fournier - Cristina Gareau - Rachid Mazroui

Fuente: https://link.springer.com/







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