Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Bloomington, IN 47405, United States.
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Bloomington, IN 47405, United States.
Curr Cancer Drug Targets. 2019;19(7):515-524. doi: 10.2174/1568009618666181018162117.
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.
热休克因子 1(HSF1)于 1984 年被发现,是热休克反应的主要调节因子。在这个经典角色中,HSF1 在细胞应激后被激活,如热休克,最终导致 HSF1 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下存活。然而,现在越来越清楚的是,HSF1 也在几种疾病中发挥重要作用,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,支持包括迁移、侵袭、增殖和癌细胞代谢在内的多种恶性特征。由于 HSF1 的这些功能和其他功能,它已被作为多种癌症类型患者预后的生物标志物进行研究。HSF1 的表达本身可以预测多种癌症类型的患者预后,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哪些标志物最能代表 HSF1 的肿瘤促进作用。此外,已经有几种尝试开发小分子抑制剂来降低 HSF1 的活性。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程度的疗效。在过去的十年中,与癌症相关的 HSF1 研究取得了巨大的进展,发现了 HSF1 的许多新功能。为了使这些发现产生临床影响,需要继续开发 HSF1 作为生物标志物或治疗靶点。