尼克洛萨米德通过影响YTHDF2抑制的乳酸代谢重编程抑制胃癌的进展
Mosheng Tang1, Yiyin Hu2, Xiaohui Zhu2
1Radiotherapy Center, Lishui People's Hospital, 15 Dazhong Road, Liandu District, Lishui 323000, Zhejiang, China.
iScience
|December 1, 2025
概括
这项研究揭示了胃癌 (GC) 涉及代谢重编程和升调乳酸代谢. 尼克洛萨米德药物向YTHDF2,通过调节代谢基因来抑制GC.
科学领域:
- 在瘤学瘤学.
- 代谢学 代谢学 代谢学
- 分子生物学分子生物学
背景情况:
- 胃癌 (GC) 是一种具有显著死亡率的侵袭性恶性瘤.
- 代谢重编程,影响葡萄糖,脂质和氨基酸通路,是GC的标志.
- 乳酸代谢和乳酸穿在GC进展中起着至关重要的作用.
研究的目的:
- 综合分析GC中的代谢变化,使用多omics方法.
- 为了研究乳酸穿在GC瘤发生中的作用.
- 评估尼克洛萨米德的治疗潜力及其在GC中涉及YTHDF2的机制.
主要方法:
- 在GC患者样本上的非目标代谢量和转录量.
- 单细胞RNA测序以分析细胞间代谢动态.
- 在体外和体内实验中评估尼克洛萨米德和YTHDF2对GC细胞的影响.
主要成果:
- 在GC中确定了显著的代谢重编程和上调的乳酸代谢.
- 在瘤上皮细胞和内皮细胞之间剖析的乳酸穿动力学.
- 证明尼克洛萨米德通过向YTHDF2,即代谢基因的关键调节器来抑制GC.
结论:
- 通过乳酸穿系统调节乳酸代谢是胃癌的关键驱动因素.
- 尼克洛萨米德通过通过YTHDF2-介导的代谢基因调节来破坏代谢重编程来发挥抗瘤作用.
- YTHDF2是GC代谢的关键调节器,将尼克洛萨米德作为胃癌的潜在治疗剂.
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
Adaptive 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
Drugs that Stabilize Microtubules
2.6K
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.6K
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

