在受限迁移期间的机械应力会导致异常的线粒分裂和c-MYC放大
Giulia Bastianello1,2, Gururaj Rao Kidiyoor1, Conor Lowndes1
1Istituto Fondazione Italiana per la Ricerca sul Cancro di Oncologia molecolare-the Associazione Italiana per la Ricerca sul Cancro Institute of Molecular Oncology, Milano 20139, Italy.
概括
来自受限细胞迁移的机械应激驱动了转移性瘤细胞中的染色体不稳定性和c-MYC放大,取代了细胞分裂检查点.
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 机械生物学 机械生物学
背景情况:
- 众所周知,受限细胞迁移会损害基因组完整性.
- 机械应力激活ATR和ATM机械传导通道.
- 转移性瘤细胞表现出增强的染色体不稳定性.
研究的目的:
- 调查转移性间歇性迁移引起的机械应激是否会导致瘤细胞中的染色体不稳定.
- 确定机械应力在覆盖细胞分裂检查点控制中的作用.
- 探索机械应力,c-MYC放大和转移之间的联系.
主要方法:
- 活细胞成像 活细胞成像
- 微流体方法是微流体的方法.
- 单细胞RNA测序 (scRNA-seq) 是一种
- 在体内瘤模型.
主要成果:
- 局限的瘤细胞分裂导致了螺旋杆失调,染色体错误分离,微核和脆弱性.
- 观察到高基因拷贝数变异和转录放松,包括c-MYC放大.
- 在体内,转移细胞显示高c-MYC表达,与放大相关.
- 检查点路径 (ATR,ATM,SAC) 是功能性的,但被机械应力所覆盖.
结论:
- 转移性迁移期间的机械压力促进了基因毒性和瘤性事件.
- 这解释了癌症无积分独立于螺旋组装检查点突变.
- 研究结果通过机械压力诱导的基因组不稳定性将c-MYC放大与转移性瘤联系起来.
相关概念视频
M-Cdk Drives Transition Into Mitosis
5.5K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.5K
Separation of Sister Chromatids
3.6K
At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
At the onset of anaphase, separase, a proteolytic enzyme, is...
3.6K
Mitogens and the Cell Cycle
6.4K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.4K
Cytoskeletal Coordination in Cell Migration
4.7K
A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
4.7K
Destabilization of Microtubules
2.7K
The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
2.7K
Meiosis vs. Mitosis
55.0K
Cell division is necessary for growth and reproduction in organisms. Mitosis aids cell growth and development by dividing somatic cells. In contrast, meiosis causes the division of germ cells and plays an essential role in sexual reproduction. Due to their unique functional requirements, mitosis and meiosis differ from each other in multiple aspects.
Before the start of mitosis and meiosis I, the cell synthesizes DNA, resulting in two homologous copies of each chromosome. DNA synthesis is...
Before the start of mitosis and meiosis I, the cell synthesizes DNA, resulting in two homologous copies of each chromosome. DNA synthesis is...
55.0K


