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cGAS-STING 细胞质 DNA 感应途径在肿瘤细胞中受 JAK2-STAT3 抑制。

cGAS-STING cytosolic DNA sensing pathway is suppressed by JAK2-STAT3 in tumor cells.

机构信息

Department of Microbiology, Immunology Programme, National University of Singapore, Singapore, 117456, Singapore.

NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, 117597, Singapore.

出版信息

Sci Rep. 2021 Mar 31;11(1):7243. doi: 10.1038/s41598-021-86644-x.

DOI:10.1038/s41598-021-86644-x
PMID:33790360
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8012641/
Abstract

Deficiencies in DNA repair and DNA degrading nucleases lead to accumulation of cytosolic DNA. cGAS is a critical DNA sensor for the detection of cytosolic DNA and subsequent activation of the STING signaling pathway. Here, we show that the cGAS-STING pathway was unresponsive to STING agonists and failed to induce type I interferon (IFN) expression in many tested human tumor cells including DU145 prostate cancer cells. Inhibition of IL-6 or the downstream JAK2/STAT3 signaling restored responsiveness to STING agonists in DU145 cells. STING activity in murine TRAMP-C2 prostate cancer cells was critical for tumor rejection and immune cell infiltration. Endogenous STING agonists including double-stranded DNA and RNA:DNA hybrids present in TRAMP-C2 cells contribute to tumor rejection, but tumor growth was further suppressed by administration of cGAMP. Intratumoral co-injections of IL-6 significantly reduced the anti-tumor effects of cGAMP. In summary, STING in tumor cells contributes to tumor rejection in prostate cancer cells, but its functions are frequently suppressed in tumor cells in part via JAK2 and STAT3 pathways.

摘要

DNA 修复和 DNA 降解核酸酶的缺陷导致细胞质 DNA 的积累。cGAS 是检测细胞质 DNA 并随后激活 STING 信号通路的关键 DNA 传感器。在这里，我们表明 cGAS-STING 途径对 STING 激动剂无反应，并且不能在许多测试的人类肿瘤细胞中诱导 I 型干扰素 (IFN) 表达，包括 DU145 前列腺癌细胞。抑制 IL-6 或下游 JAK2/STAT3 信号通路可恢复 DU145 细胞对 STING 激动剂的反应性。在小鼠 TRAMP-C2 前列腺癌细胞中，STING 活性对于肿瘤排斥和免疫细胞浸润至关重要。TRAMP-C2 细胞中存在的内源性 STING 激动剂，包括双链 DNA 和 RNA:DNA 杂种，有助于肿瘤排斥，但 cGAMP 的给药进一步抑制了肿瘤生长。肿瘤内共注射 IL-6 可显著降低 cGAMP 的抗肿瘤作用。总之，肿瘤细胞中的 STING 有助于前列腺癌细胞的肿瘤排斥，但通过 JAK2 和 STAT3 途径，其功能经常受到抑制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9614/8012641/081c4af1218f/41598_2021_86644_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9614/8012641/082a840781f3/41598_2021_86644_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9614/8012641/1eedb9d80244/41598_2021_86644_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9614/8012641/70a5f1e9fd92/41598_2021_86644_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9614/8012641/f2558f6e7ca2/41598_2021_86644_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9614/8012641/081c4af1218f/41598_2021_86644_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9614/8012641/082a840781f3/41598_2021_86644_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9614/8012641/1eedb9d80244/41598_2021_86644_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9614/8012641/70a5f1e9fd92/41598_2021_86644_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9614/8012641/f2558f6e7ca2/41598_2021_86644_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9614/8012641/081c4af1218f/41598_2021_86644_Fig5_HTML.jpg

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本文引用的文献

1
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2
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Oncoimmunology. 2020 Jun 16;9(1):1777624. doi: 10.1080/2162402X.2020.1777624.
3
The Cytosolic DNA-Sensing cGAS-STING Pathway in Cancer.细胞质 DNA 感应 cGAS-STING 通路在癌症中的作用。
Human RNase H2 upregulation counteracts oncogene- and chemotherapy-induced replication stress.
人核糖核酸酶H2的上调可抵消癌基因和化疗诱导的复制应激。
Oncogene. 2025 Jul 10. doi: 10.1038/s41388-025-03489-8.
4
Carriers Multimerize STING Protein Fragments to Activate Type I Interferon Signaling in STING-Deficient Cancer Cells.载体使STING蛋白片段多聚化以激活STING缺陷癌细胞中的I型干扰素信号传导。
Mol Pharm. 2025 Aug 4;22(8):4632-4650. doi: 10.1021/acs.molpharmaceut.5c00226. Epub 2025 Jul 6.
5
The role of type I interferon signaling in myeloid anti-tumor immunity.I型干扰素信号在髓系抗肿瘤免疫中的作用。
Front Immunol. 2025 Mar 3;16:1547466. doi: 10.3389/fimmu.2025.1547466. eCollection 2025.
6
Induction of translation-suppressive G3BP1 stress granules and interferon-signaling cGAS condensates by transfected plasmid DNA.转染的质粒DNA诱导翻译抑制性G3BP1应激颗粒和干扰素信号cGAS凝聚物的形成。
Hlife. 2025 Jan;3(1):21-37. doi: 10.1016/j.hlife.2024.11.005. Epub 2024 Dec 24.
7
Interleukin-6 deficiency reduces neuroinflammation by inhibiting the STAT3-cGAS-STING pathway in Alzheimer's disease mice.白细胞介素-6 缺乏通过抑制阿尔茨海默病小鼠中的 STAT3-cGAS-STING 通路减少神经炎症。
J Neuroinflammation. 2024 Nov 1;21(1):282. doi: 10.1186/s12974-024-03277-3.
8
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RNA Biol. 2024 Jan;21(1):25-35. doi: 10.1080/15476286.2024.2408708. Epub 2024 Sep 26.
9
Cyclic GMP-AMP synthase recognizes the physical features of DNA.环状GMP-AMP合酶识别DNA的物理特征。
Acta Pharmacol Sin. 2025 Feb;46(2):264-270. doi: 10.1038/s41401-024-01369-7. Epub 2024 Aug 7.
10
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Nucleic Acids Res. 2024 Sep 9;52(16):9630-9653. doi: 10.1093/nar/gkae654.
Cancer Discov. 2020 Jan;10(1):26-39. doi: 10.1158/2159-8290.CD-19-0761. Epub 2019 Dec 18.
4
STAT3 inhibition enhances CDN-induced STING signaling and antitumor immunity.抑制 STAT3 可增强 CDN 诱导的 STING 信号转导和抗肿瘤免疫。
Cancer Lett. 2019 May 28;450:110-122. doi: 10.1016/j.canlet.2019.02.029. Epub 2019 Feb 18.
5
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Cancer Discov. 2019 Jan;9(1):34-45. doi: 10.1158/2159-8290.CD-18-0689. Epub 2018 Oct 8.
6
RIG-I and IL-6 are negative-feedback regulators of STING induced by double-stranded DNA.RIG-I和IL-6是由双链DNA诱导的STING的负反馈调节因子。
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7
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Biochem Biophys Res Commun. 2016 Sep 30;478(4):1764-71. doi: 10.1016/j.bbrc.2016.09.021. Epub 2016 Sep 5.
8
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Immunity. 2016 May 17;44(5):1177-89. doi: 10.1016/j.immuni.2016.04.010. Epub 2016 May 10.
9
The Where, the When, and the How of Immune Monitoring for Cancer Immunotherapies in the Era of Checkpoint Inhibition.在检查点抑制时代，癌症免疫疗法的免疫监测的地点、时间和方法。
Clin Cancer Res. 2016 Apr 15;22(8):1865-74. doi: 10.1158/1078-0432.CCR-15-1507.
10
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Cell Rep. 2016 Jan 12;14(2):282-97. doi: 10.1016/j.celrep.2015.12.029. Epub 2015 Dec 31.