دورية أكاديمية
cGAS-STING signalling in cancer: striking a balance with chromosomal instability.
العنوان: | cGAS-STING signalling in cancer: striking a balance with chromosomal instability. |
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المؤلفون: | Beernaert B; Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, U.K., Parkes EE; Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, U.K. |
المصدر: | Biochemical Society transactions [Biochem Soc Trans] 2023 Apr 26; Vol. 51 (2), pp. 539-555. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Review |
اللغة: | English |
بيانات الدورية: | Publisher: Portland Press On The Behalf Of The Biochemical Society Country of Publication: England NLM ID: 7506897 Publication Model: Print Cited Medium: Internet ISSN: 1470-8752 (Electronic) Linking ISSN: 03005127 NLM ISO Abbreviation: Biochem Soc Trans Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : Portland Press On The Behalf Of The Biochemical Society |
مواضيع طبية MeSH: | Chromosomal Instability* , Neoplasms*/genetics , Neoplasms*/metabolism, Humans ; Immunity, Innate/genetics ; Inflammation ; Nucleotidyltransferases ; Signal Transduction ; Tumor Microenvironment |
مستخلص: | Chromosomal instability (CIN) is a hallmark of cancer that drives tumour evolution. It is now recognised that CIN in cancer leads to the constitutive production of misplaced DNA in the form of micronuclei and chromatin bridges. These structures are detected by the nucleic acid sensor cGAS, leading to the production of the second messenger 2'3'-cGAMP and activation of the critical hub of innate immune signalling STING. Activation of this immune pathway should instigate the influx and activation of immune cells, resulting in the eradication of cancer cells. That this does not universally occur in the context of CIN remains an unanswered paradox in cancer. Instead, CIN-high cancers are notably adept at immune evasion and are highly metastatic with typically poor outcomes. In this review, we discuss the diverse facets of the cGAS-STING signalling pathway, including emerging roles in homeostatic processes and their intersection with genome stability regulation, its role as a driver of chronic pro-tumour inflammation, and crosstalk with the tumour microenvironment, which may collectively underlie its apparent maintenance in cancers. A better understanding of the mechanisms whereby this immune surveillance pathway is commandeered by chromosomally unstable cancers is critical to the identification of new vulnerabilities for therapeutic exploitation. (© 2023 The Author(s).) |
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معلومات مُعتمدة: | 224623/Z/21/Z United Kingdom WT_ Wellcome Trust; C2195/A31281 United Kingdom CRUK_ Cancer Research UK |
فهرسة مساهمة: | Keywords: DNA synthesis and repair; cGAS-STING; chromosomal instability; immunosurveillance; innate immunity |
المشرفين على المادة: | EC 2.7.7.- (Nucleotidyltransferases) EC 2.7.7.- (cGAS protein, human) 0 (STING1 protein, human) |
تواريخ الأحداث: | Date Created: 20230306 Date Completed: 20230515 Latest Revision: 20230527 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC10212549 |
DOI: | 10.1042/BST20220838 |
PMID: | 36876871 |
قاعدة البيانات: | MEDLINE |
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