癌症中的 Hsp70：生存与死亡之战中的双重代理,Journal of Cellular Physiology

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癌症中的 Hsp70：生存与死亡之战中的双重代理
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-11-10 , DOI: 10.1002/jcp.30132
Mehdi A Vostakolaei _{1,

2} , Leila Hatami-Baroogh ₃ , Ghader Babaei ₄ , Ommoleila Molavi ₅ , Shirafkan Kordi _{6,

7} , Jalal Abdolalizadeh _{8,

9}

Affiliation

热休克蛋白 (Hsps) 超家族，也称为分子伴侣，高度保守，存在于所有生物体中，在蛋白质命运中起着至关重要的作用。HspA1A (Hsp70-1)，在本综述中称为 Hsp70，在大多数未受应激的正常细胞中以低水平或检测不到的水平表达，但大量研究表明，不同类型的肿瘤细胞在质膜上表达 Hsp70，导致对程序性细胞死亡和肿瘤进展。Hsp70 以三种形式释放到细胞外环境中，包括游离可溶性、与癌抗原肽复合和外泌体形式。因此，它似乎是人类恶性肿瘤的一个有前途的治疗靶点。然而，大量研究表明细胞内和细胞外Hsp70具有双重功能。一系列证据表明，细胞内 Hsp70 通过抑制细胞凋亡和溶酶体细胞死亡 (LCD) 具有细胞保护功能，以及细胞外 Hsp70 可以促进肿瘤发生和血管生成。其他证据表明细胞内 Hsp70 可以促进细胞凋亡，膜相关/细胞外 Hsp70 可以引发抗肿瘤先天性和适应性免疫反应。鉴于这些相互矛盾的功能，作为“双重药剂”，Hsp70 能否成为未来靶向癌症治疗的有前途的工具？为了回答这个问题，在这篇综述中，除了针对 Hsp70 的抑制和刺激策略及其挑战之外，我们还将讨论 Hsp70 在癌症中的功能。

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Hsp70 in cancer: A double agent in the battle between survival and death

The heat shock protein (Hsps) superfamily, also known as molecular chaperones, are highly conserved and present in all living organisms and play vital roles in protein fate. The HspA1A (Hsp70‐1), called Hsp70 in this review, is expressed at low or undetectable levels in most unstressed normal cells, but numerous studies have shown that diverse types of tumor cells express Hsp70 at the plasma membrane that leads to resistance to programmed cell death and tumor progression. Hsp70 is released into the extracellular milieu in three forms including free soluble, complexed with cancer antigenic peptides, and exosome forms. Therefore, it seems to be a promising therapeutic target in human malignancies. However, a great number of studies have indicated that both intracellular and extracellular Hsp70 have a dual function. A line of evidence presented that intracellular Hsp70 has a cytoprotective function via suppression of apoptosis and lysosomal cell death (LCD) as well as that extracellular Hsp70 can promote tumorigenesis and angiogenesis. Other evidence showed intracellular Hsp70 can promote apoptosis and membrane‐associated/extracellular Hsp70 can elicit antitumor innate and adaptive immune responses. Given the contradictory functions, as a "double agent," could Hsp70 be a promising tool in the future of targeted cancer therapies? To answer this question, in this review, we will discuss the functions of Hsp70 in cancers besides inhibition and stimulation strategies for targeting Hsp70 along with their challenges.

更新日期：2020-11-10

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