Guscott Molly, Saha Akash, Maharaj Jovanna, McClelland Sarah E
Barts Cancer Institute, Queen Mary University of London, London, UK.
Barts Cancer Institute, Queen Mary University of London, London, UK.
Int J Biochem Cell Biol. 2022 Nov;152:106300. doi: 10.1016/j.biocel.2022.106300. Epub 2022 Sep 20.
Within most tumour types, cancerous cells exist in a state of aneuploidy, an incorrect chromosome number or structure. Additionally, tumour cells frequently exhibit chromosomal instability; the ongoing loss or gain of whole or parts of chromosomes during cell division. Chromosomal instability results in a high rate of chromosome segregation defects, and a constantly changing genomic landscape. A second consequence of recurrent chromosome segregation defects is the exclusion of mis-segregated chromatin from the newly reforming nucleus. Chromosomes, or chromosome fragments that are not incorporated into the main nucleus are often packaged into extranuclear structures called micronuclei. While the initial impact of micronucleus formation is an imbalance or loss of genetic material in the resulting daughter cells, several other downstream consequences are now known to result from this process. In this review, we discuss the further consequences of micronucleus formation, including how structural changes to the micronuclear envelope, and the rupturing of micronuclear membranes can contribute to metastasis, immune cell activation and overall, tumour progression.
在大多数肿瘤类型中，癌细胞处于非整倍体状态，即染色体数目或结构错误。此外，肿瘤细胞经常表现出染色体不稳定；在细胞分裂过程中持续出现整条或部分染色体的丢失或增加。染色体不稳定导致染色体分离缺陷率很高，以及基因组格局不断变化。反复出现的染色体分离缺陷的另一个后果是将错误分离的染色质排除在新形成的细胞核之外。未并入主核的染色体或染色体片段通常被包装成称为微核的核外结构。虽然微核形成的最初影响是导致子代细胞中遗传物质的不平衡或丢失，但现在已知这个过程还会产生其他几个下游后果。在这篇综述中，我们讨论微核形成的进一步后果，包括微核膜的结构变化以及微核膜破裂如何促进转移、免疫细胞激活以及总体上的肿瘤进展。
