Neutrophils and micronuclei: An emerging link between genomic instability and cancer-driven inflammation

IF 1.5 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2022-01-01 DOI:10.1016/j.mrfmmm.2022.111778

Triet M. Bui, Ronen Sumagin

{"title":"Neutrophils and micronuclei: An emerging link between genomic instability and cancer-driven inflammation","authors":"Triet M. Bui, Ronen Sumagin","doi":"10.1016/j.mrfmmm.2022.111778","DOIUrl":null,"url":null,"abstract":"<div>Two recent studies by Bui and Butin-Israeli et al. have established the novel contribution of neutrophils to genomic instability induction and aberrant shaping of the DNA repair landscape, particularly observed in patients with inflammatory bowel diseases (IBD) and/or progressive colorectal cancer (CRC). In addition, these back-to-back studies uncovered a sharp increase in the numbers of micronuclei and lagging chromosomes in pre-cancerous and cancerous epithelium in response to prolonged PMN exposure. Given the emerging link between neutrophils and micronuclei as well as the established role of micronuclei in cGAS/STING activation, this special commentary aims to elaborate on the mechanisms by which CRC cells may adapt to neutrophil-driven genomic instability while concurrently sustain an inflamed tumor niche. We postulate that such tumor microenvironment with constant immune cell presence, inflammatory milieu, and cumulative DNA damage can drive tumor adaptation and resistance to therapeutic interventions. Finally, we discuss potential novel therapeutic approaches that can be leveraged to target this emerging neutrophil-micronuclei pathological axis, thereby preventing perpetual CRC inflammation and unwanted tumor adaptation.</div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"824 ","pages":"Article 111778"},"PeriodicalIF":1.5000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0027510722000057","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}

引用次数: 1

Abstract

Two recent studies by Bui and Butin-Israeli et al. have established the novel contribution of neutrophils to genomic instability induction and aberrant shaping of the DNA repair landscape, particularly observed in patients with inflammatory bowel diseases (IBD) and/or progressive colorectal cancer (CRC). In addition, these back-to-back studies uncovered a sharp increase in the numbers of micronuclei and lagging chromosomes in pre-cancerous and cancerous epithelium in response to prolonged PMN exposure. Given the emerging link between neutrophils and micronuclei as well as the established role of micronuclei in cGAS/STING activation, this special commentary aims to elaborate on the mechanisms by which CRC cells may adapt to neutrophil-driven genomic instability while concurrently sustain an inflamed tumor niche. We postulate that such tumor microenvironment with constant immune cell presence, inflammatory milieu, and cumulative DNA damage can drive tumor adaptation and resistance to therapeutic interventions. Finally, we discuss potential novel therapeutic approaches that can be leveraged to target this emerging neutrophil-micronuclei pathological axis, thereby preventing perpetual CRC inflammation and unwanted tumor adaptation.

查看原文本刊更多论文

中性粒细胞和微核:基因组不稳定性和癌症驱动炎症之间的新联系

Bui和butin - israel等人最近的两项研究确定了中性粒细胞对基因组不稳定性诱导和DNA修复景观异常形成的新贡献，特别是在炎症性肠病(IBD)和/或进行性结直肠癌(CRC)患者中观察到。此外，这些背靠背的研究发现，在长期暴露于PMN的情况下，癌前和癌上皮中微核和滞后染色体的数量急剧增加。鉴于中性粒细胞和微核之间的新联系以及微核在cGAS/STING激活中的既定作用，本专题评论旨在阐述CRC细胞可能适应中性粒细胞驱动的基因组不稳定性，同时维持炎症肿瘤生态位的机制。我们假设这种具有恒定免疫细胞存在、炎症环境和累积DNA损伤的肿瘤微环境可以驱动肿瘤适应和抵抗治疗干预。最后，我们讨论了潜在的新的治疗方法，可以利用这一新兴的中性粒细胞-微核病理轴，从而防止永久的结直肠癌炎症和不必要的肿瘤适应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 生物-毒理学

CiteScore

4.90

自引率

0.00%

发文量

审稿时长

51 days

期刊介绍： Mutation Research (MR) provides a platform for publishing all aspects of DNA mutations and epimutations, from basic evolutionary aspects to translational applications in genetic and epigenetic diagnostics and therapy. Mutations are defined as all possible alterations in DNA sequence and sequence organization, from point mutations to genome structural variation, chromosomal aberrations and aneuploidy. Epimutations are defined as alterations in the epigenome, i.e., changes in DNA methylation, histone modification and small regulatory RNAs. MR publishes articles in the following areas: Of special interest are basic mechanisms through which DNA damage and mutations impact development and differentiation, stem cell biology and cell fate in general, including various forms of cell death and cellular senescence. The study of genome instability in human molecular epidemiology and in relation to complex phenotypes, such as human disease, is considered a growing area of importance. Mechanisms of (epi)mutation induction, for example, during DNA repair, replication or recombination; novel methods of (epi)mutation detection, with a focus on ultra-high-throughput sequencing. Landscape of somatic mutations and epimutations in cancer and aging. Role of de novo mutations in human disease and aging; mutations in population genomics. Interactions between mutations and epimutations. The role of epimutations in chromatin structure and function. Mitochondrial DNA mutations and their consequences in terms of human disease and aging. Novel ways to generate mutations and epimutations in cell lines and animal models.