结直肠癌细胞中 STING 信号的失调抑制了 DNA 损伤反应，并与肿瘤发生相关。
Deregulation of STING Signaling in Colorectal Carcinoma Constrains DNA Damage Responses and Correlates With Tumorigenesis.
机构信息
Department of Cell Biology and the Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Department of Cell Biology and the Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
出版信息
Cell Rep. 2016 Jan 12;14(2):282-97. doi: 10.1016/j.celrep.2015.12.029. Epub 2015 Dec 31.
Abstract
Stimulator of interferon genes (STING) has been shown to be critical for controlling antiviral responses as well as anti-tumor adaptive immunity, but little is known regarding its regulation in human tumors. Here, we report that STING signaling is recurrently suppressed in a wide variety of cancers, including colorectal carcinoma. Loss of STING signaling impeded DNA damage responses accountable for generating key cytokines that facilitate tissue repair and anti-tumor T cell priming, such as type I interferons (IFNs). Correspondingly, defective STING function was also highly predictive of effectual DNA-virus-mediated oncolytic activity. Thus, impaired STING responses may enable damaged cells to evade host immunosurveillance processes, although they provide a critical prognostic measurement that could help predict the outcome of effective oncoviral therapy.
摘要
干扰素基因刺激物 (STING) 已被证明对于控制抗病毒反应以及抗肿瘤适应性免疫至关重要，但关于其在人类肿瘤中的调节知之甚少。在这里，我们报告说，STING 信号在多种癌症中经常受到抑制，包括结直肠癌。STING 信号的丢失会阻碍 DNA 损伤反应，从而产生关键细胞因子，促进组织修复和抗肿瘤 T 细胞启动，如 I 型干扰素 (IFN)。相应地，有缺陷的 STING 功能也高度预测有效的 DNA 病毒介导的溶瘤活性。因此，受损的 STING 反应可能使受损细胞逃避宿主免疫监视过程，尽管它们提供了一个关键的预后测量，可以帮助预测有效的溶瘤病毒治疗的结果。
相似文献
1
Deregulation of STING Signaling in Colorectal Carcinoma Constrains DNA Damage Responses and Correlates With Tumorigenesis.结直肠癌细胞中 STING 信号的失调抑制了 DNA 损伤反应，并与肿瘤发生相关。
Cell Rep. 2016 Jan 12;14(2):282-97. doi: 10.1016/j.celrep.2015.12.029. Epub 2015 Dec 31.
2
Suppression of STING signaling through epigenetic silencing and missense mutation impedes DNA damage mediated cytokine production.通过表观遗传沉默和错义突变抑制 STING 信号传导会阻碍 DNA 损伤介导的细胞因子产生。
Oncogene. 2018 Apr;37(15):2037-2051. doi: 10.1038/s41388-017-0120-0. Epub 2018 Jan 25.
3
Recurrent Loss of STING Signaling in Melanoma Correlates with Susceptibility to Viral Oncolysis.黑色素瘤中 STING 信号的反复缺失与对病毒溶瘤的易感性相关。
Cancer Res. 2016 Nov 15;76(22):6747-6759. doi: 10.1158/0008-5472.CAN-16-1404. Epub 2016 Sep 28.
4
Diverse roles of STING-dependent signaling on the development of cancer.STING依赖性信号传导在癌症发展中的多种作用。
Oncogene. 2015 Oct 8;34(41):5302-8. doi: 10.1038/onc.2014.457. Epub 2015 Feb 2.
5
The emerging role of stimulator of interferons genes signaling in sepsis: Inflammation, autophagy, and cell death.干扰素基因信号转导刺激物在脓毒症中的新作用：炎症、自噬和细胞死亡。
Acta Physiol (Oxf). 2019 Mar;225(3):e13194. doi: 10.1111/apha.13194. Epub 2018 Oct 22.
6
CSN6 deregulation impairs genome integrity in a COP1-dependent pathway.CSN6失调通过一种依赖COP1的途径损害基因组完整性。
Oncotarget. 2015 May 20;6(14):11779-93. doi: 10.18632/oncotarget.3151.
7
New perspectives on type I IFNs in cancer.癌症中I型干扰素的新视角。
Cytokine Growth Factor Rev. 2015 Apr;26(2):175-8. doi: 10.1016/j.cytogfr.2015.01.001. Epub 2015 Jan 7.
8
Wnt/β-catenin signaling regulated SATB1 promotes colorectal cancer tumorigenesis and progression.Wnt/β-连环蛋白信号传导调控的SATB1促进结直肠癌的肿瘤发生和进展。
Oncogene. 2016 Mar 31;35(13):1679-91. doi: 10.1038/onc.2015.232. Epub 2015 Jul 13.
9
Lanatoside C suppressed colorectal cancer cell growth by inducing mitochondrial dysfunction and increased radiation sensitivity by impairing DNA damage repair.毛花苷丙通过诱导线粒体功能障碍抑制结肠癌细胞生长，并通过损害DNA损伤修复增加放射敏感性。
Oncotarget. 2016 Feb 2;7(5):6074-87. doi: 10.18632/oncotarget.6832.
10
Fusobacterium nucleatum and T Cells in Colorectal Carcinoma.具核梭杆菌与结直肠癌中的 T 细胞
JAMA Oncol. 2015 Aug;1(5):653-61. doi: 10.1001/jamaoncol.2015.1377.
引用本文的文献
1
Advances in nanomaterials for enhancing cGAS-STING pathway mediated anti-tumor treatment.用于增强cGAS-STING通路介导的抗肿瘤治疗的纳米材料研究进展
Mater Today Bio. 2025 Aug 11;34:102190. doi: 10.1016/j.mtbio.2025.102190. eCollection 2025 Oct.
2
Novel anti-HER2 nanobody-drug conjugates with enhanced penetration of solid tumor and BBB, reduced systemic exposure and superior antitumor efficacy.新型抗HER2纳米抗体-药物偶联物，具有增强的实体瘤和血脑屏障穿透能力、降低的全身暴露水平以及卓越的抗肿瘤疗效。
Acta Pharmacol Sin. 2025 Aug 18. doi: 10.1038/s41401-025-01634-3.
3
Mutations in genes encoding innate immune molecules identified in bladder cancer samples as potential biomarkers for immunotherapy with BCG and agonists.在膀胱癌样本中鉴定出的编码天然免疫分子的基因突变，作为卡介苗和激动剂免疫治疗的潜在生物标志物。
Front Urol. 2023 Mar 20;3:984967. doi: 10.3389/fruro.2023.984967. eCollection 2023.
4
Advances in Oncolytic Viral Therapy in Melanoma: A Comprehensive Review.溶瘤病毒疗法在黑色素瘤治疗中的进展：全面综述
Vaccines (Basel). 2025 Jul 3;13(7):727. doi: 10.3390/vaccines13070727.
5
The human STING agonist E7766 induces immunogenic tumor clearance, independent of tumor-intrinsic STING expression in the murine model of sarcoma.人类STING激动剂E7766可诱导免疫原性肿瘤清除，在肉瘤小鼠模型中与肿瘤内在的STING表达无关。
Oncoimmunology. 2025 Dec;14(1):2534912. doi: 10.1080/2162402X.2025.2534912. Epub 2025 Jul 22.
6
Unveiling cGAS mechanisms: Insights into DNA damage and immune sensing in cancer.揭示cGAS机制：对癌症中DNA损伤与免疫传感的见解
DNA Repair (Amst). 2025 Jul 9;152:103868. doi: 10.1016/j.dnarep.2025.103868.
7
Combination of LowDose Epigenetic Modifiers and TIC10 for the Activation of Antitumor Immunity and Inhibition of Tumor Growth in Gastrointestinal Cancer.低剂量表观遗传修饰剂与TIC10联合用于激活抗肿瘤免疫及抑制胃肠道肿瘤生长
Cancer Med. 2025 Jul;14(14):e71061. doi: 10.1002/cam4.71061.
8
Ongoing genome doubling shapes evolvability and immunity in ovarian cancer.持续的基因组加倍塑造了卵巢癌的进化能力和免疫特性。
Nature. 2025 Jul 16. doi: 10.1038/s41586-025-09240-3.
9
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.
10
DNA methylation protects cancer cells against senescence.DNA甲基化可保护癌细胞免于衰老。
Nat Commun. 2025 Jul 1;16(1):5901. doi: 10.1038/s41467-025-61157-7.
本文引用的文献
1
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency.错配修复缺陷肿瘤中的程序性死亡受体-1阻断
N Engl J Med. 2015 Jun 25;372(26):2509-20. doi: 10.1056/NEJMoa1500596. Epub 2015 May 30.
2
Direct Activation of STING in the Tumor Microenvironment Leads to Potent and Systemic Tumor Regression and Immunity.肿瘤微环境中STING的直接激活导致强效且全身性的肿瘤消退和免疫。
Cell Rep. 2015 May 19;11(7):1018-30. doi: 10.1016/j.celrep.2015.04.031. Epub 2015 May 7.
3
STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade.含STING激动剂的癌症疫苗可治愈对PD-1阻断疗法耐药的已形成肿瘤。
Sci Transl Med. 2015 Apr 15;7(283):283ra52. doi: 10.1126/scitranslmed.aaa4306.
4
The STING pathway and the T cell-inflamed tumor microenvironment.干扰素基因刺激蛋白（STING）信号通路与T细胞炎症性肿瘤微环境
Trends Immunol. 2015 Apr;36(4):250-6. doi: 10.1016/j.it.2015.02.003. Epub 2015 Mar 7.
5
Diverse roles of STING-dependent signaling on the development of cancer.STING依赖性信号传导在癌症发展中的多种作用。
Oncogene. 2015 Oct 8;34(41):5302-8. doi: 10.1038/onc.2014.457. Epub 2015 Feb 2.
6
STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors.依赖于STING的胞质DNA传感促进免疫原性肿瘤中辐射诱导的I型干扰素依赖性抗肿瘤免疫。
Immunity. 2014 Nov 20;41(5):843-52. doi: 10.1016/j.immuni.2014.10.019. Epub 2014 Nov 6.
7
STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors.依赖于干扰素基因刺激蛋白（STING）的胞质DNA传感介导免疫原性肿瘤的固有免疫识别。
Immunity. 2014 Nov 20;41(5):830-42. doi: 10.1016/j.immuni.2014.10.017. Epub 2014 Nov 5.
8
TroVax in colorectal cancer.TroVax用于结直肠癌治疗。
Hum Vaccin Immunother. 2014;10(11):3196-200. doi: 10.4161/21645515.2014.973323.
9
Self-DNA, STING-dependent signaling and the origins of autoinflammatory disease.自身 DNA、STING 依赖性信号转导与自身炎症性疾病的起源。
Curr Opin Immunol. 2014 Dec;31:121-6. doi: 10.1016/j.coi.2014.10.009. Epub 2014 Nov 4.
10
The role of the microbiota in inflammation, carcinogenesis, and cancer therapy.微生物群在炎症、癌变和癌症治疗中的作用。
Eur J Immunol. 2015 Jan;45(1):17-31. doi: 10.1002/eji.201444972. Epub 2014 Nov 13.
Zotero 插件