核胺支持WNT驱动的超扩散和瘤启动
Georgios Kanellos1, Chiara Giacomelli2, Alexander Raven2
1Cancer Research UK Scotland Institute, Glasgow, UK. g.kanellos@crukscotlandinstitute.ac.uk.
Nature genetics
|December 18, 2025
概括
核胺 (NPM1) 通过抑制压力反应来支持WNT驱动的癌症. 抑制NPM1可能是WNT驱动瘤的治疗策略,特别是在结直肠癌中.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症遗传学 癌症遗传学
背景情况:
- 核胺 (NPM1) 是一种核蛋白,涉及到造血性恶性瘤,在固体瘤中过度表达.
- 它在固体瘤进展中的功能作用,特别是在WNT驱动的癌症中,仍然不清楚.
研究的目的:
- 调查NPM1在WNT驱动的肠道和肝脏瘤发生中的作用.
- 阐明NPM1影响癌症进展和综合应激反应的分子机制.
主要方法:
- 研究了在APC损失后对WNT敏感组织中的NPM1表达.
- 分析了NPM1损失对蛋白质合成,核糖体功能和p53激活的影响.
- 与人类结直肠癌 (CRC) 中的WNT信号传递,扩散和TP53状态相关的NPM1表达和删除.
主要成果:
- 在APC损失后,NPM1被上调,并促进WNT驱动的瘤发生.
- 失去NPM1会触发核糖体暂停,整合应激反应和p53激活,从而产生抗瘤作用.
- 在CRC中,NPM1的表达与WNT信号传递和扩散相关;NPM1的缺失与TP53的失活有关.
结论:
- NPM1是一个关键的WNT效应因子,通过减弱综合应激反应和p53激活来维持高增殖和瘤发生.
- 对于成年人上皮质平衡来说,NPM1是不可或缺的,这使得它成为p53-proficient WNT驱动的瘤 (如耐火性KRAS突变CRC和肝癌) 的潜在治疗标.
相关概念视频
02:23Abnormal 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
02:54Canonical Wnt Signaling Pathway
10.3K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.3K
02:55The Nucleolus
10.2K
The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
10.2K
03:03mTOR 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
01:41Non-Canonical Wnt Signaling Pathways
8.2K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.2K
02:53Adaptive Mechanisms in Cancer Cells
6.9K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.9K