Hikeshi能成为热疗的潜在靶点吗?

Y. Tabuchi, Tatsuya Yunoki
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引用次数: 0

摘要

虽然热疗(HT)是一种很有前途的癌症治疗方式,但使用高温疗法的主要困难是由于热休克蛋白(HSPs)的升高而导致的热耐受性的发展,热休克蛋白作为分子伴侣。在这些热休克蛋白中,Hsp70具有细胞保护活性,在耐热性的获得中起关键作用。热应激时,Hsp70迅速从细胞质转移到细胞核。最近,蛋白质Hikeshi,也被称为C11orf73的基因产物,已被证明在热胁迫条件下作为Hsp70的核输入载体发挥作用。Hikeshi基因的敲除显著增强了人类癌细胞在热应激存在(而不是不存在)的情况下对高温疗法和轻度高温疗法的敏感性。此外,Hikeshi在人胃癌或肾癌中表达上调。也有人认为,导致hikashi错义突变p. Cys4Ser或p. Val54Leu纯合的功能缺陷分别导致芬兰人或德系犹太人患者患上脑白质病。本文综述了Hikeshi的生理和病理作用,并讨论了其作为HT治疗靶点的潜力。
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Can be Hikeshi a Potential Target for Hyperthermic Therapy?
: While hyperthermia (HT) is a promising modality for cancer therapy, major difficulty with the use of HT is the development of thermotolerance due to the elevation of heat shock proteins (HSPs), which function as molecular chaperons. Among the HSPs, Hsp70 possesses cytoprotective activity and plays a critical role in the acquisition of thermotolerance. Upon heat stress, Hsp70 rapidly translocates from the cytoplasm to nucleus. Recently, the protein Hikeshi, also known as the gene product of C11orf73, has been shown to function as a nuclear import carrier of Hsp70 under heat-stress conditions. Knockdown of Hikeshi significantly enhances sensitivity to HT and mild HT in the presence — but not the absence — of heat-stress in human cancer cells. Moreover, upregulation of Hikeshi expression is observed in human gastric or renal cancer. It has also been suggested that functional defects leading to homozygosity for a missense mutation, p. Cys4Ser or p. Val54Leu, in Hikeshi cause leukoencephalopathy in Finnish or Ashkenazi-Jewish patients, respectively. This review summarizes the physiological and pathological roles of Hikeshi and discusses its potential as a target in HT therapy.
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