FGFR1突变的同时发生调节了神经质神经瘤的瘤发生
Jacopo Boni1,2, Míriam Fernández-González1,3, HyeRim Han1,3
1Bellvitge Biomedical Research Institute (IDIBELL), Avinguda de la Granvia de l'Hospitalet 199, 08908 L'hospitalet de Llobregat, Barcelona, Spain.
The EMBO journal
|November 1, 2025
概括
纤维细胞生长因子受体1 (FGFR1) 突变通过逃避细胞降解来驱动脑瘤的生长. 一种特定的变体 (R661P) 通过恢复退化,影响细胞命运,作为瘤抑制剂.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- FGFR1遗传变化与大脑恶性瘤有关,特别是低度质神经元瘤.
- 多个FGFR1事件表明,在低突变的环境中,驱动瘤发展的内在机制.
研究的目的:
- 在脑瘤中阐明FGFR1突变并发的分子机制.
- 研究特定FGFR1变异对瘤发生和细胞行为的功能影响.
主要方法:
- 使用BioID-MS.对野生类型,单基因和双基因突变FGFR1蛋白的近接互动组映射.
- 功能性测试评估细胞自我更新和基因表达变化.
主要成果:
- 确定了FGFR1热点突变 (N546K,K656E) 的致癌作用,与抗 lysosomal 降解相关.
- 在R661P变体中表现出抑制瘤的功能,该变体可以挽救受体退化并调节下游信号.
- 表明R661P消除了寡头质瘤细胞的自我更新,并改变神经发育基因表达,由瘤基因突变逆转效应.
结论:
- 在脑瘤中,FGFR1的改变具有上下文依赖的瘤效应.
- 热点突变和易感变体之间的相互作用影响瘤进展和细胞命运.
- 这些发现提供了关于FGFR1在低突变负担,未经治疗的瘤中的作用的见解.
相关概念视频
The Retinoblastoma Gene
4.6K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.6K
Cancer-Critical Genes I: Proto-oncogenes
11.1K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
11.1K
Abnormal Proliferation
5.1K
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...
5.1K


