UMP作为NR4A1的内源调节剂,以控制胃癌的进展
Guodi Cai1, Zhenhua Zhang1, Lin Zhong2
1National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Molecular cell
|November 21, 2025
概括
尿素单酸盐 (UMP) 调节了胃癌中的NR4A1. 足够的UMP促进癌症,而缺乏则激活NR4A1抑制瘤生长,提供了一种新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 重编程核酸代谢对于瘤进展至关重要.
- 癌细胞感知核酸水平的机制尚未完全理解.
研究的目的:
- 在胃癌中识别核酸感应的内源调节剂.
- 研究孤儿核受体NR4A1在胃癌进展和核酸代谢中的作用.
主要方法:
- 确定UMP作为NR4A1.1.的直接绑定合作伙伴.
- 研究了UMP水平对NR4A1活性和胃癌细胞行为 in vitro和 in vivo的影响.
- 评估了NR4A1激动剂和针对de novo胺基生物合成 (DNPB) 和NR4A1.1的联合治疗策略的影响.
主要成果:
- 在UMP充足的情况下,UMP直接与NR4A1结合,抑制其瘤抑制功能.
- 缺乏UMP激活NR4A1,导致通过超强增强器重编程和增强的线粒体亡抑制胃癌细胞存活和进展.
- 当DNPB被抑制时,NR4A1激动剂抑制了金胺救援通路.
- 同时准DNPB和NR4A1在胃癌模型中显示出协同的瘤致死性.
结论:
- 在胃癌中,UMP作为NR4A1的内源调节剂.
- NR4A1在感知核酸水平和调节胃癌细胞命运方面发挥着至关重要的作用.
- 联合向DNPB和NR4A1为胃癌提供了一个有前途的治疗策略.
相关概念视频
mTOR Signaling and Cancer Progression
4.6K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
4.6K
Hormonal Regulation
47.7K
Hormones regulate a significant portion of digestion through activation of the neuroendocrine system. The neuroendocrine system of digestion contains many different hormones all with multiple functions that are both, directly and indirectly, involved in digestion.
47.7K
Mitogens and the Cell Cycle
7.7K
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...
7.7K
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.4K
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...
2.4K
Transducer Mechanism: Nuclear Receptors
2.3K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
2.3K
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


