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信号转导与转录激活因子1(STAT1)在卵巢癌中的双重作用:对分子机制及应用潜力的洞察

The Dual Role of STAT1 in Ovarian Cancer: Insight Into Molecular Mechanisms and Application Potentials.

作者信息

Li Xin, Wang Fanchen, Xu Xiaolin, Zhang Jinguo, Xu Guoxiong

机构信息

Research Center for Clinical Medicine, Jinshan Hospital, Fudan University, Shanghai, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

Front Cell Dev Biol. 2021 Mar 23;9:636595. doi: 10.3389/fcell.2021.636595. eCollection 2021.

Abstract

The signal transducer and activator of transcription 1 (STAT1) is a transducer protein and acts as a transcription factor but its role in ovarian cancer (OC) is not completely understood. Practically, there are two-faced effects of STAT1 on tumorigenesis in different kinds of cancers. Existing evidence reveals that STAT1 has both tumor-suppressing and tumor-promoting functions involved in angiogenesis, cell proliferation, migration, invasion, apoptosis, drug resistance, stemness, and immune responses mainly through interacting and regulating target genes at multiple levels. The canonical STAT1 signaling pathway shows that STAT1 is phosphorylated and activated by the receptor-activated kinases such as Janus kinase in response to interferon stimulation. The STAT1 signaling can also be crosstalk with other signaling such as transforming growth factor-β signaling involved in cancer cell behavior. OC is often diagnosed at an advanced stage due to symptomless or atypical symptoms and the lack of effective detection at an early stage. Furthermore, patients with OC often develop chemoresistance and recurrence. This review focuses on the multi-faced role of STAT1 and highlights the molecular mechanisms and biological functions of STAT1 in OC.

摘要

信号转导与转录激活因子1(STAT1)是一种转导蛋白,作为转录因子发挥作用,但其在卵巢癌(OC)中的作用尚未完全明确。实际上,STAT1在不同类型癌症的肿瘤发生过程中具有两面性作用。现有证据表明,STAT1主要通过在多个水平上与靶基因相互作用并进行调控,在血管生成、细胞增殖、迁移、侵袭、凋亡、耐药性、干性和免疫反应等方面具有肿瘤抑制和肿瘤促进功能。经典的STAT1信号通路显示,在干扰素刺激下,STAT1会被受体激活激酶(如Janus激酶)磷酸化并激活。STAT1信号也可与其他信号通路(如参与癌细胞行为的转化生长因子-β信号通路)发生相互作用。由于症状不明显或不典型以及缺乏早期有效的检测手段,OC往往在晚期才被诊断出来。此外,OC患者常出现化疗耐药和复发的情况。本综述聚焦于STAT1的多面作用,并着重阐述其在OC中的分子机制和生物学功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5c4/8021797/2520a0300596/fcell-09-636595-g001.jpg

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