新生皮里米丁合成是NF2缺陷美索瘤的附带代谢脆弱性
Duo Xu1, Yanyun Gao2,3, Shengchen Liu4
1Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. xuduo@jsph.org.cn.
EMBO molecular medicine
|July 24, 2025
概括
间皮质瘤中NF2的损失通过促进皮里米丁合成来促进癌症的生长. 这种代谢脆弱性为NF2缺陷的多叶膜间皮瘤提供了一个新的治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 代谢途径 代谢途径
背景情况:
- 腹半径质瘤 (PM) 是一种致命的癌症,由于其复杂的基因组和异质性,治疗选择不佳.
- 在PM中代谢变化的分子基础,特别是瘤抑制基因 (TSG) 失活如何驱动瘤发生,尚不清楚.
研究的目的:
- 研究由TSG无活化驱动的PM中代谢重编程的分子机制.
- 为了确定NF2-缺少的PM亚型中的特定代谢依赖.
主要方法:
- 对多性间皮瘤样本的综合多性分析.
- 关于NF2,YAP,CAD和DHODH在癌细胞增殖中的功能性研究.
- 在体外和体内实验来评估代谢依赖性的实验.
主要成果:
- NF2功能丧失定义了一个独特的PM亚型,具有增强的de novopyrimidine合成.
- 缺乏NF2的PM细胞对这种增殖途径具有关键的依赖性.
- 失去NF2会激活YAP,从而对关键的金胺合成酶CAD和DHODH进行上调.
结论:
- 胺新生合成是NF2缺陷半质瘤中一个关键的代谢漏洞.
- 针对这种途径为NF2缺乏PM提供了一个潜在的合成致命治疗策略.
- 这项研究为PM代谢重编程和潜在干预提供了新的见解.
更多相关视频
09:37Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021
1.9K
08:57Author Spotlight: Genetically Engineered Mouse Models and Pathological Characterization of Neurofibromatosis Type 1 Associated Tumors
Published on: May 17, 2024
2.1K
相关概念视频
Biosynthesis of Nucleic Acids
178
Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
178
Nucleotide Excision Repair
3.8K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.8K
Mismatch Repair
5.2K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
5.2K
Long-patch Base Excision Repair
7.2K
Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
7.2K
NF-κB-dependent Signaling Pathway
7.9K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.9K
Abnormal Proliferation
4.6K
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...
4.6K
