染色体结构和物理收缩在表型切换和癌细胞扩散方面进行合作
bioRxiv : the preprint server for biology
|February 12, 2026
概括
转移性黑色素瘤细胞经历表观遗传和结构性核变化,由机械压力和异色素蛋白损失驱动. 这些适应增强了侵入性和转移潜力,提供了新的治疗点.
科学领域:
- 癌症生物学 癌症生物学
- 细胞力学 细胞力学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 现型可塑性驱动癌症转移和治疗耐药性.
- 介质细胞样 (MES) 现型与转录程序 (如AP1/TEAD) 有关.
- 瘤细胞上的机械力量会在传播过程中影响核分子拥挤.
研究的目的:
- 研究机械压力,核架构和转录程序在驱动MES身份和转移性适应中的相互作用.
- 在皮肤黑色素瘤中,MES表型背后的显微色素组织特征.
主要方法:
- 集成的体外和体内表观遗传学分析.
- 细胞系和患者样本的纳米尺度成像.
- 分析染色体组织,CTCF定位和异染色体标记 (H3K9me3).
主要成果:
- MES细胞表现出CTCF从域边界迁移到EMT类基因的调节区域,减少绝缘和扩展TADs.
- 在MES细胞中,核形状的重新连接和异色色素的损失支持可变形性.
- 物理收缩会诱导类似于MES的染色质特征,并促进转移.
- 抑制H3K9me3会触发MES特征并增加侵入性.
结论:
- 转移性能力涉及表观遗传和结构性核重编程,使基因网络转移和物理适应性成为可能.
- 核架构的改变在机制上与瘤的攻击性行为有关.
- 结果确定了潜在的生物标志物和治疗点,以拦截转移性进展.
相关概念视频
Inheritance of Chromatin Structures
7.6K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
7.6K
Cooperative Allosteric Transitions
8.9K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
8.9K
Cooperative Allosteric Transitions
3.1K
3.1K
Cooperative Allosteric Transitions
2.7K
2.7K
Cooperative Binding of Transcription Regulators
7.4K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
7.4K
Chromatin Position Affects Gene Expression
24.9K
Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
24.9K


