Endoplasmic Reticulum (ER) malfunction, leading to ER stress, can be a consequence of genome instability and hypoxic tissue environments. Cancer cells survive by acquiring or enhancing survival mechanisms to counter the effects of ER stress and these homeostatic responses may represent new therapeutic targets. Understanding the links between ER stress and apoptosis may be approached using drugs to specifically target ER stress responses in cancer cells. Currently there is considerable clinical interest in the use of two ER stress inducing agents, fenretinide (FenR,a synthetic retinoid) and velcade (a 26S proteasome inhibitor) for the treatment of neuroectodermal tumours. Both agents induce potent apoptosis of both neuroblastoma and melanoma cells together with inducing the ER stress response genes ERdj5, ERp57, GRP78, calreticulin and calnexin. Since ERdj5 and ERp57 are induced as a consequence of ER stress, the aim of this study was to test the hypothesis that knockdown of these homeostatic response genes would increase the efficacy of either fenretinide or velcade

Combining homeostatic mechanisms of ER Stress to increase susceptibility of cancer cell to ER stress-induced apoptosis: The role of stress proteins ERdj5 and ERp57

CORAZZARI, MARCO;
2007-01-01

Abstract

Endoplasmic Reticulum (ER) malfunction, leading to ER stress, can be a consequence of genome instability and hypoxic tissue environments. Cancer cells survive by acquiring or enhancing survival mechanisms to counter the effects of ER stress and these homeostatic responses may represent new therapeutic targets. Understanding the links between ER stress and apoptosis may be approached using drugs to specifically target ER stress responses in cancer cells. Currently there is considerable clinical interest in the use of two ER stress inducing agents, fenretinide (FenR,a synthetic retinoid) and velcade (a 26S proteasome inhibitor) for the treatment of neuroectodermal tumours. Both agents induce potent apoptosis of both neuroblastoma and melanoma cells together with inducing the ER stress response genes ERdj5, ERp57, GRP78, calreticulin and calnexin. Since ERdj5 and ERp57 are induced as a consequence of ER stress, the aim of this study was to test the hypothesis that knockdown of these homeostatic response genes would increase the efficacy of either fenretinide or velcade
2007
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11579/80821
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