Verfaillie Tom, Salazar Maria, Velasco Guillermo, Agostinis Patrizia
Department of Molecular Cell Biology, Cell Death Research and Therapy Laboratory, Faculty of Medicine, Catholic University of Leuven, 3000 Leuven, Belgium.
Int J Cell Biol. 2010;2010:930509. doi: 10.1155/2010/930509. Epub 2010 Jan 17.
Different physiological and pathological conditions can perturb protein folding in the endoplasmic reticulum, leading to a condition known as ER stress. ER stress activates a complex intracellular signal transduction pathway, called unfolded protein response (UPR). The UPR is tailored essentially to reestablish ER homeostasis also through adaptive mechanisms involving the stimulation of autophagy. However, when persistent, ER stress can switch the cytoprotective functions of UPR and autophagy into cell death promoting mechanisms. Recently, a variety of anticancer therapies have been linked to the induction of ER stress in cancer cells, suggesting that strategies devised to stimulate its prodeath function or block its prosurvival function, could be envisaged to improve their tumoricidial action. A better understanding of the molecular mechanisms that determine the final outcome of UPR and autophagy activation by chemotherapeutic agents, will offer new opportunities to improve existing cancer therapies as well as unravel novel targets for cancer treatment.
不同的生理和病理状况会扰乱内质网中的蛋白质折叠，导致一种称为内质网应激的状态。内质网应激会激活一条复杂的细胞内信号转导通路，称为未折叠蛋白反应（UPR）。未折叠蛋白反应本质上是通过涉及自噬刺激的适应性机制来重新建立内质网稳态。然而，持续的内质网应激会将未折叠蛋白反应和自噬的细胞保护功能转变为促进细胞死亡的机制。最近，多种抗癌疗法与癌细胞内质网应激的诱导有关，这表明可以设想设计刺激其促死亡功能或阻断其促生存功能的策略，以改善它们的杀肿瘤作用。更好地理解决定化疗药物激活未折叠蛋白反应和自噬最终结果的分子机制，将为改善现有癌症疗法以及揭示癌症治疗的新靶点提供新机会。
