Manipulation of JAK/STAT Signalling by High-Risk HPVs: Potential Therapeutic Targets for HPV-Associated Malignancies.
Manipulation of JAK/STAT Signalling by High-Risk HPVs: Potential Therapeutic Targets for HPV-Associated Malignancies.
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DOI：
10.3390/v12090977
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发表时间：
2020-09-03
期刊：
影响因子：
--
通讯作者：
Macdonald A
中科院分区：
文献类型：
--
作者：
Morgan EL;Macdonald A
人乳头瘤病毒（HPV）是一种小型DNA病毒，可导致约5%的人类癌症，包括几乎所有的宫颈癌病例和相当比例的肛门生殖器癌和口腔癌。HPV癌蛋白E5、E6和E7操纵细胞信号通路以逃避免疫应答并促进病毒持续存在。Janus激酶/信号转导子和转录激活子（JAK/STAT）通路已经成为广泛的重要生物信号传导通路中的关键介质，包括细胞增殖、细胞存活和免疫应答。虽然STAT 1和STAT 2主要驱动由干扰素引发的免疫信号传导，但STAT 3和STAT 5已广泛与许多癌症的存活和增殖潜力相关。因此，STAT 3和STAT 5的抑制可以在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信号转导以逃避免疫系统并促进细胞增殖，从而使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，以及这些方法如何可能用于治疗HPV相关疾病。
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.
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