Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Sciences, Hebei Normal University, Shijiazhuang, Hebei 050024, China.
Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Sciences, Hebei Normal University, Shijiazhuang, Hebei 050024, China.
Biochim Biophys Acta Rev Cancer. 2020 Aug;1874(1):188390. doi: 10.1016/j.bbcan.2020.188390. Epub 2020 Jul 9.
Heat shock factor 1 (HSF1) systematically guards proteome stability and proteostasis by regulating the expression of heat shock protein (HSP), thus rendering cancer cells addicted to HSF1. The non-canonical transcriptional programme driven by HSF1, which is distinct from the heat shock response (HSR), plays an indispensable role in the initiation, promotion and progression of cancer. Therefore, HSF1 is widely exploited as a potential therapeutic target in a broad spectrum of cancers. Various molecules and signals in the cell jointly regulate the activation and attenuation of HSF1. The high-level expression of HSF1 in tumours and its relationship with patient prognosis imply that HSF1 can be used as a biomarker for patient prognosis and a target for cancer treatment. In this review, we discuss the newly identified mechanisms of HSF1 activation and regulation, the diverse functions of HSF1 in tumourigenesis, and the feasibility of using HSF1 as a prognostic marker. Disrupting cancer cell proteostasis by targeting HSF1 represents a novel anti-cancer therapeutic strategy.
热休克因子 1（HSF1）通过调节热休克蛋白（HSP）的表达，系统地保护蛋白质组的稳定性和蛋白质平衡，从而使癌细胞对 HSF1 产生依赖。由 HSF1 驱动的非典型转录程序与热休克反应（HSR）不同，在癌症的发生、促进和进展中发挥不可或缺的作用。因此，HSF1 被广泛开发为广谱癌症的潜在治疗靶点。细胞中的各种分子和信号共同调节 HSF1 的激活和衰减。肿瘤中 HSF1 的高水平表达及其与患者预后的关系表明，HSF1 可作为患者预后的生物标志物和癌症治疗的靶点。在这篇综述中，我们讨论了 HSF1 激活和调节的新机制、HSF1 在肿瘤发生中的多种功能，以及将 HSF1 用作预后标志物的可行性。通过靶向 HSF1 破坏癌细胞的蛋白质平衡代表了一种新的抗癌治疗策略。
