Targeting Hsp70: A possible therapy for cancer.
Targeting Hsp70: A possible therapy for cancer.
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DOI：
10.1016/j.canlet.2016.01.056
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发表时间：
2016-04-28
期刊：
影响因子：
9.7
通讯作者：
Mishra M
中科院分区：
文献类型：
--
作者：
Kumar S;Stokes J 3rd;Singh UP;Scissum Gunn K;Acharya A;Manne U;Mishra M
在所有生物体中，热休克蛋白（HSPs）提供了一种古老的防御系统。这些蛋白质作为分子伴侣，帮助正确折叠和重新折叠错误折叠的蛋白质，并帮助消除衰老和受损的细胞。包括Hsp100、Hsp90、Hsp70、Hsp40和小Hsp40。通过其底物结合域，Hsp70与广泛的分子相互作用，从未折叠到天然折叠和聚集的蛋白质，并对各种细胞应激提供细胞保护作用。在病理生理条件下，高表达Hsp70可使细胞在致死性损伤下存活。升高的Hsp70通过在凋亡信号通路的几个点上相互作用，导致细胞凋亡的抑制。肿瘤细胞中Hsp70的表达升高可能通过提供对化疗的抗性而导致肿瘤的发生和进展。相反，抑制或敲低Hsp70可减小肿瘤的大小并使其完全消退。此外，细胞外Hsp70作为免疫原参与MHC-I分子的交叉呈递。本综述的目的是研究Hsp70在癌症中的作用，并提出针对Hsp70的癌症治疗策略。
In all organisms, heat-shock proteins (HSPs) provide an ancient defense system. These proteins act as molecular chaperones by assisting proper folding and refolding of misfolded proteins and aid in the elimination of old and damaged cells. HSPs include Hsp100, Hsp90, Hsp70, Hsp40, and small HSPs. Through its substrate-binding domains, Hsp70 interacts with wide spectrum of molecules, ranging from unfolded to natively folded and aggregated proteins, and provides cytoprotective role against various cellular stresses. Under pathophysiological conditions, the high expression of Hsp70 allows cells to survive with lethal injuries. Increased Hsp70, by interacting at several points on apoptotic signaling pathways, leads to inhibition of apoptosis. Elevated expression of Hsp70 in cancer cells may be responsible for tumorigenesis and for tumor progression by providing resistance to chemotherapy. In contrast, inhibition or knockdown of Hsp70 reduces the size of tumors and can cause their complete regression. Moreover, extracellular Hsp70 acts as an immunogen that participates in cross presentation of MHC-I molecules. The goals of this review are to examine the roles of Hsp70 in cancer and to present strategies targeting Hsp70 in the development of cancer therapeutics.
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影响因子：
4.8
作者：
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DOI：
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发表时间：
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期刊：
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