Boudesco Christophe, Cause Sebastien, Jego Gaëtan, Garrido Carmen
Univ. Bourgogne Franche-Comté, LNC UMR1231, Dijon, France.
INSERM, LNC UMR1231, Dijon, France.
Methods Mol Biol. 2018;1709:371-396. doi: 10.1007/978-1-4939-7477-1_27.
Heat shock protein 70 (Hsp70) is the most ubiquitous stress-inducible chaperone. It accumulates in the cells in response to a wide variety of physiological and environmental insults including anticancer chemotherapy, thus allowing the cell to survive to lethal conditions. Intracellular Hsp70 is viewed as a cytoprotective protein. Indeed, this protein can inhibit key effectors of the apoptotic and autophagy machineries. In cancer cells, the expression of Hsp70 is abnormally high, and Hsp70 may participate in oncogenesis and in resistance to chemotherapy. In rodent models, Hsp70 overexpression increases tumor growth and metastatic potential. Depletion or inhibition of Hsp70 frequently reduces the size of the tumors and can even cause their complete involution. However, HSP70 is also found in the extra-cellular space where it may signal via membrane receptors or endosomes to alter gene transcription and cellular function. Overall, Hsp70 extracellular function is believed to be immnunogenic and the term chaperokine to define the extracellular chaperones such as Hsp70 has been advanced. In this chapter the knowledge to date, as well as some emerging paradigms about the intra- and extra-cellular functions of Hsp70, are presented. The strategies targeting Hsp70 that are being developed in cancer therapy will also be discussed.
热休克蛋白70（Hsp70）是最普遍存在的应激诱导伴侣蛋白。它在细胞中积累以应对包括抗癌化疗在内的多种生理和环境损伤，从而使细胞能够在致死条件下存活。细胞内的Hsp70被视为一种细胞保护蛋白。事实上，这种蛋白可以抑制凋亡和自噬机制的关键效应器。在癌细胞中，Hsp70的表达异常高，并且Hsp70可能参与肿瘤发生和化疗耐药。在啮齿动物模型中，Hsp70的过表达会增加肿瘤生长和转移潜能。Hsp70的缺失或抑制常常会减小肿瘤的大小，甚至可导致肿瘤完全消退。然而，HSP70也存在于细胞外空间，在那里它可能通过膜受体或内体发出信号，以改变基因转录和细胞功能。总体而言，Hsp70的细胞外功能被认为具有免疫原性，并且已经提出了“伴侣趋化因子”这一术语来定义诸如Hsp70之类的细胞外伴侣蛋白。在本章中，将介绍迄今为止关于Hsp70细胞内和细胞外功能的知识以及一些新出现的范例。还将讨论癌症治疗中正在开发的针对Hsp70的策略。
