Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Adv Exp Med Biol. 2020;1243:69-85. doi: 10.1007/978-3-030-40204-4_5.
Heat Shock Factor 1 (HSF1), the master transcriptional regulator of the heat shock response (HSR), was first cloned more than 30 years ago. Most early research interrogating the role that HSF1 plays in biology focused on its cytoprotective functions, as a factor that promotes the survival of organisms by protecting against the proteotoxicity associated with neurodegeneration and other pathological conditions. However, recent studies have revealed a deleterious role of HSF1, as a factor that is co-opted by cancer cells to promote their own survival to the detriment of the organism. In cancer, HSF1 operates in a multifaceted manner to promote oncogenic transformation, proliferation, metastatic dissemination, and anti-cancer drug resistance. Here we review our current understanding of HSF1 activation and function in malignant progression and discuss the potential for HSF1 inhibition as a novel anticancer strategy. Collectively, this ever-growing body of work points to a prominent role of HSF1 in nearly every aspect of carcinogenesis.
热休克因子 1（HSF1）是热休克反应（HSR）的主要转录调节因子，它在 30 多年前被首次克隆。大多数早期研究探究 HSF1 在生物学中的作用的研究都集中在其细胞保护功能上，作为一种通过对抗与神经退行性变和其他病理状况相关的蛋白毒性来促进生物体生存的因子。然而，最近的研究揭示了 HSF1 的有害作用，它被癌细胞利用来促进自身的生存，从而损害了生物体。在癌症中，HSF1 以多种方式发挥作用，促进致癌转化、增殖、转移扩散和抗癌药物耐药性。在这里，我们回顾了我们目前对 HSF1 在恶性进展中的激活和功能的理解，并讨论了抑制 HSF1 作为一种新的抗癌策略的潜力。总的来说，这一不断增长的研究工作表明 HSF1 在肿瘤发生的几乎所有方面都起着重要作用。
