TRIM37与EZH2相互作用,以表观遗传抑制PTCH1并通过声波刺途径调节质瘤干细胞中的干细胞
Lize Cai1, Yongsheng Liu1, Yanyan Li1
1Neurosurgery and Brain and Nerve Research Laboratory, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Journal of neuro-oncology
|June 17, 2024
概括
通过与EZH2相互作用,TRIM37促进质母细胞瘤的生长和茎状,这种相互作用激活了Sonic Hedgehog通路. 针对TRIM37提供了一个潜在的治疗策略,用于多种质母细胞瘤 (GBM).
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 干细胞研究 干细胞研究
背景情况:
- 质瘤干细胞 (GSCs) 驱动多种质母细胞瘤 (GBM) 耐治疗.
- 已知TRIM37的致癌作用,但其在质瘤和GSC中的机制尚不清楚.
研究的目的:
- 阐明TRIM37在调节质瘤和GSC生长中的作用.
- 在GBM中研究TRIM37和EZH2之间的相互作用.
主要方法:
- 基因表达分析 (西式涂抹,RT-qPCR,免疫光).
- 细胞活力和亡试验 (CCK-8,流细胞计).
- 蛋白相互作用研究 (Co-IP) 和途径分析 (双化酶记者测定,ChIP).
- 在体内验证使用质瘤小鼠模型.
主要成果:
- TRIM37表达在GSC中升高,并促进它们的生长,干性和亡耐药性.
- 在核中,TRIM37与EZH2相互作用.
- TRIM37和EZH2的共同抑制降低了Sonic Hedgehog (SHH) 途径的调节.
- EZH2在表观遗传上抑制了PTCH1,激活了GSC中的SHH通路.
结论:
- 通过EZH2相互作用,TRIM37维持了GSC的生长和茎状.
- EZH2通过降低PTCH1.1的调节来激活SHH通路.
- TRIM37代表了GBM的潜在治疗标.
相关概念视频
Hedgehog Signaling Pathway
7.3K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.3K
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.1K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K
Epigenetic Regulation
3.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.0K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.2K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
Interactions Between Signaling Pathways
6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K


