Tumour Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA.
School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, West Yorkshire, UK.
Viruses. 2020 Sep 3;12(9):977. doi: 10.3390/v12090977.
Human papillomaviruses (HPVs) are small, DNA viruses that cause around 5% of all cancers in humans, including almost all cervical cancer cases and a significant proportion of anogenital and oral cancers. The HPV oncoproteins E5, E6 and E7 manipulate cellular signalling pathways to evade the immune response and promote virus persistence. The Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway has emerged as a key mediator in a wide range of important biological signalling pathways, including cell proliferation, cell survival and the immune response. While STAT1 and STAT2 primarily drive immune signalling initiated by interferons, STAT3 and STAT5 have widely been linked to the survival and proliferative potential of a number of cancers. As such, the inhibition of STAT3 and STAT5 may offer a therapeutic benefit in HPV-associated cancers. In this review, we will discuss how HPV manipulates JAK/STAT signalling to evade the immune system and promote cell proliferation, enabling viral persistence and driving cancer development. We also discuss approaches to inhibit the JAK/STAT pathway and how these could potentially be used in the treatment of HPV-associated disease.
人乳头瘤病毒（HPV）是小型 DNA 病毒，可导致人类约 5%的癌症，包括几乎所有宫颈癌病例以及相当一部分肛门生殖器和口腔癌。HPV 致癌蛋白 E5、E6 和 E7 操纵细胞信号通路，逃避免疫反应并促进病毒持续存在。Janus 激酶/信号转导和转录激活因子（JAK/STAT）通路已成为广泛的重要生物学信号通路中的关键介质，包括细胞增殖、细胞存活和免疫反应。虽然 STAT1 和 STAT2 主要驱动干扰素引发的免疫信号，但 STAT3 和 STAT5 广泛与多种癌症的存活和增殖潜力相关。因此，抑制 STAT3 和 STAT5 可能在 HPV 相关癌症中提供治疗益处。在这篇综述中，我们将讨论 HPV 如何操纵 JAK/STAT 信号通路以逃避免疫系统并促进细胞增殖，从而实现病毒持续存在并推动癌症发展。我们还讨论了抑制 JAK/STAT 通路的方法以及这些方法如何在治疗 HPV 相关疾病中得到应用。
