Neutrophils and micronuclei: An emerging link between genomic instability and cancer-driven inflammation.
Neutrophils and micronuclei: An emerging link between genomic instability and cancer-driven inflammation.
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DOI：
10.1016/j.mrfmmm.2022.111778
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发表时间：
2022-01
影响因子：
2.3
通讯作者：
Sumagin, Ronen
中科院分区：
文献类型：
--
作者：
Bui, Triet M.;Sumagin, Ronen
Bui和Butin-伊斯雷尔等人最近的两项研究。已经确定了中性粒细胞对基因组不稳定诱导和DNA修复格局的异常塑造的新贡献，特别是在炎症性肠病(IBD)和/或进展性结直肠癌(CRC)患者中观察到。此外，这些背靠背的研究发现，随着PMN暴露时间的延长，癌前病变和癌前病变上皮中微核和落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出现的联系，以及微核在cGAS/STING激活中的既定作用，这篇特别评论旨在阐述CRC细胞可能通过哪些机制适应中性粒细胞驱动的基因组不稳定性，同时同时维持炎症的肿瘤生态位。我们推测，这种具有持续免疫细胞存在、炎症环境和累积DNA损伤的肿瘤微环境可以驱动肿瘤对治疗干预的适应性和抵抗力。最后，我们讨论了潜在的新的治疗方法，可以被用来针对这个新出现的中性粒细胞-微核病理轴，从而防止永久性的结直肠癌炎症和不想要的肿瘤适应。
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.
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影响因子：
29.4
作者：
Boland CR;Goel A
通讯作者：
Goel A
影响因子：
29.4
作者：
Bui, Triet M.;Butin-Israeli, Veronika;Sumagin, Ronen
通讯作者：
Sumagin, Ronen
影响因子：
8
作者：
Huang, L;Snyder, AR;Morgan, WF
通讯作者：
Morgan, WF
影响因子：
--
作者：
Kemp DM;Pidich A;Larijani M;Jonas R;Lash E;Sato T;Terai M;De Pizzol M;Allegretti M;Igoucheva O;Alexeev V
通讯作者：
Alexeev V
影响因子：
7.3
作者：
Constanzo J;Faget J;Ursino C;Badie C;Pouget JP
通讯作者：
Pouget JP