染色体不稳定引起的细胞入侵通过卡斯巴酶驱动的DNA损伤
Lara Barrio1, Ana-Elena Gaspar1, Mariana Muzzopappa1
1Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
Current biology : CB
|September 26, 2023
概括
染色体不稳定性 (CIN) 通过导致DNA损伤来驱动癌症的侵入性. 这项研究揭示了效应器卡斯帕斯和JAK/STAT通路放大了这种损伤,促进了转移.
科学领域:
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
- 癌症研究 癌症研究
背景情况:
- 染色体不稳定性 (CIN) 与人类癌症转移的增加有关.
- 驱动CIN诱导的侵入性的机制尚未完全理解.
研究的目的:
- 用Drosophila模型研究DNA损伤和特定分子途径在CIN诱导的癌症侵入性中的作用.
- 为了确定转移的新型治疗点.
主要方法:
- 利用Drosophila上皮模型来研究CIN.
- 分析了DNA损伤,酶活性和JAK/STAT信号.
- 研究了细胞因子Upd3在自克林反循环中的作用.
主要成果:
- 由于落后的染色体和复制性压力导致的CIN诱导的DNA损伤,促进了侵入性.
- 效应器卡斯帕斯在增强CIN诱导的DNA损伤方面具有次致命作用.
- 通过JAK/STAT通路,通过亲细胞亡的基因诱导激活了细胞亡的卡斯帕.
- 一个Upd3介导的自环放大了迁移细胞中的亡信号,增强了侵入性.
结论:
- 通过染色体分离错误和随后的DNA损伤,CIN促进转移.
- 由Upd3放大的效应器卡斯帕和JAK/STAT通路是CIN诱导入侵性的关键媒介.
- 这些发现突显了CIN在转移中的染色体签名独立的影响.
相关概念视频
DNA Damage can Stall the Cell Cycle
9.2K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.2K
Caspases
12.6K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
12.6K
Cancer Cell Migration through Invadopodia
2.3K
Invadosome is a broad category of cell surface structures with proteolytic activity that degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
2.3K
The Intrinsic Apoptotic Pathway
6.6K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.6K
Overview of DNA Repair
31.1K
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
31.1K
DNA Damage Can Stall the Cell Cycle
2.6K
2.6K


