Hsp70: A Cancer Target Inside and Outside the Cell
Hsp70: A Cancer Target Inside and Outside the Cell
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DOI：
10.1007/978-1-4939-7477-1_27
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发表时间：
2018-01-01
期刊：
影响因子：
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通讯作者：
Garrido, Carmen
中科院分区：
文献类型：
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作者：
Boudesco, Christophe;Cause, Sebastien;Garrido, Carmen
热休克蛋白70（Heat shock protein 70，Hsp70）是最普遍存在的应激诱导分子伴侣。它在细胞中积累，以响应各种生理和环境的侮辱，包括抗癌化疗，从而使细胞存活到致命的条件。细胞内Hsp70被认为是一种细胞保护蛋白。事实上，这种蛋白质可以抑制细胞凋亡和自噬机制的关键效应子。在癌细胞中，Hsp70的表达异常高，并且Hsp70可能参与肿瘤发生和对化疗的抵抗。在啮齿动物模型中，Hsp70过表达增加肿瘤生长和转移潜力。Hsp70的消耗或抑制常常减小肿瘤的大小，甚至可以导致它们完全退化。然而，HSP 70也存在于细胞外空间，在那里它可以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细胞外功能被认为是免疫原性的，并且用于定义细胞外伴侣如Hsp70的术语伴侣因子已被提出。在这一章中，知识的日期，以及一些新兴的范式内和细胞外的Hsp70的功能，提出。针对Hsp70正在开发的癌症治疗策略也将进行讨论。
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.