Inserm, UMR866, Faculty of Medicine, 7 Boulevard Jeanne D'Arc, F-21000 Dijon, France.
Exp Cell Res. 2012 Sep 10;318(15):1946-58. doi: 10.1016/j.yexcr.2012.05.012. Epub 2012 May 28.
Inducible heat shock proteins are molecular chaperones whose expression is increased after many different types of stress. They have a protective function helping the cell to cope with lethal conditions. Their basal expression is low in nonstressed, normal and nontransformed cells. However, in cancer cells and particularly in hematological malignancies, they are surprisingly abundant. Malignant cells have to rewire their metabolic requirements and therefore have a higher need for chaperones. This cancer cell addiction for HSPs is the basis for the use of HSP inhibitors in cancer therapy. HSPs have been shown to interact with different key apoptotic proteins. As a result, HSPs can essentially block the apoptotic pathways at several steps, most of them involving the activation of cystein proteases called caspases. Apoptosis and differentiation are physiological processes that share many common features, for instance, a controlled caspase activation and chromatin condensation are frequently observed. It is, therefore, not surprising that HSPs may be implicated in the differentiation process. HSPs may determine the fate of the cells by orchestrating the decision of apoptosis versus differentiation. This review will focus on the role of HSPs in hematological malignancies and the emerging therapeutic options that are being either proposed or used to target these protective proteins.
诱导热休克蛋白是分子伴侣，其表达在多种应激后增加。它们具有保护功能，帮助细胞应对致命条件。在非应激、正常和非转化细胞中，它们的基础表达水平较低。然而，在癌细胞中，特别是在血液恶性肿瘤中，它们异常丰富。恶性细胞必须重新调整其代谢需求，因此对伴侣蛋白的需求更高。癌细胞对 HSP 的这种依赖是 HSP 抑制剂在癌症治疗中的应用基础。已经表明 HSP 与不同的关键凋亡蛋白相互作用。结果，HSP 可以在多个步骤上基本阻断凋亡途径，其中大多数涉及称为半胱氨酸蛋白酶的胱天蛋白酶的激活。凋亡和分化是具有许多共同特征的生理过程，例如，经常观察到受控的半胱天冬酶激活和染色质浓缩。因此，HSP 可能参与分化过程并不奇怪。HSP 可以通过协调细胞凋亡与分化的决策来决定细胞的命运。这篇综述将重点介绍 HSP 在血液恶性肿瘤中的作用，以及正在提出或用于靶向这些保护蛋白的新兴治疗选择。
