HSF1 as a Cancer Biomarker and Therapeutic Target.
HSF1 as a Cancer Biomarker and Therapeutic Target.
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HSF1作为癌症生物标志物和治疗靶标。
DOI：
10.2174/1568009618666181018162117
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发表时间：
2019
影响因子：
3
通讯作者：
Gökmen-Polar Y
中科院分区：
文献类型：
--
作者：
Carpenter RL;Gökmen-Polar Y
热休克因子1（HSF 1）是1984年发现的热休克反应的主要调节因子。在这一经典作用中，HSF 1在细胞应激（如热休克）后被激活，最终导致HSF 1介导的热休克蛋白表达，以保护蛋白质组并在这些急性应激中存活。然而，现在越来越清楚的是，HSF1在几种疾病中也起着重要作用，也许没有比癌症更突出的了。HSF1似乎在癌症中具有多效性作用，其支持恶性肿瘤的多个方面，包括迁移、侵袭、增殖和癌细胞代谢等。由于HSF1的这些功能和其他功能，它已被研究为多种癌症类型患者预后的生物标志物。在多种癌症类型中，单独的HSF1表达可预测患者的预后，但在其他情况下，HSF1活性的标志物更具预测性。显然，需要进一步的工作来梳理出哪些标志物最能代表HSF 1的肿瘤促进作用。此外，已经有几次尝试开发小分子抑制剂以降低HSF 1活性。所有这些HSF1抑制剂仍处于临床前模型中，但在抑制肿瘤生长方面显示出不同水平的功效。在过去的十年中，与癌症中的HSF 1相关的研究的增长是巨大的，其中沿着发现了HSF 1的许多新功能。为了使这些发现产生临床影响，需要继续进一步开发HSF 1作为生物标志物或治疗靶点。
Heat shock factor 1 (HSF1) was discovered in 1984 as the master regulator of the heat shock response. In this classical role, HSF1 is activated following cellular stresses such as heat shock that ultimately lead to HSF1-mediated expression of heat shock proteins to protect the proteome and survive these acute stresses. However, it is now becoming clear that HSF1 also plays a significant role in several diseases, perhaps none more prominent than cancer. HSF1 appears to have a pleiotropic role in cancer by supporting multiple facets of malignancy including migration’ invasion, proliferation, and cancer cell metabolism among others. Because of these functions, and others, of HSF1, it has been investigated as a biomarker for patient outcomes in multiple cancer types. HSF1 expression alone was predictive for patient outcomes in multiple cancer types but in other instances, markers for HSF1 activity were more predictive. Clearly, further work is needed to tease out which markers are most representative of the tumor promoting effects of HSF1. Additionally, there have been several attempts at developing small molecule inhibitors to reduce HSF1 activity. All of these HSF1 inhibitors are still in preclinical models but have shown varying levels of efficacy at suppressing tumor growth. The growth of research related to HSF1 in cancer has been enormous over the last decade with many new functions of HSF1 discovered along the way. In order for these discoveries to reach clinical impact, further development of HSF1 as a biomarker or therapeutic target needs to be continued.