肠道微生物代谢物通过铁灭抑制促进结直肠癌的发展
Weiwei Cui1, Meng Guo2, Dong Liu1
1Department of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Nature cell biology
|January 3, 2024
概括
一种肠道细菌代谢物 - - 转-3-烯酸 (IDA) - - 通过激活烯酸碳水化合物受体 (AHR) 来促进结直肠癌. 针对这种IDA-AHR-ALDH1A3通路可能为与铁死相关的CRC提供新的治疗方法.
科学领域:
- 微生物学 微生物学
- 在瘤学瘤学.
- 代谢学 代谢学 代谢学
背景情况:
- 肠道微生物群影响人类健康和疾病,包括癌症.
- 微生物代谢物可以促进瘤发生,但机制往往不清楚.
- 结肠直肠癌 (CRC) 的进展与特定的肠道细菌有关.
研究的目的:
- 调查Peptostreptococcus anaerobius衍生型酸代谢物 - - 转-3-内烯酸 (IDA) 在结直肠癌发生过程中的作用.
- 阐明IDA促进CRC的分子机制.
- 确定与铁死相关的CRC的潜在治疗点.
主要方法:
- 在体外和体内实验中使用细胞系和小鼠模型进行实验 (异种移植,ApcMin/+).
- 对IDA与酸受体 (AHR) 和化脱酶1家族成员A3 (ALDH1A3) 的相互作用进行分析.
- 在CRC患者中P.无氧生物丰富的量化.
主要成果:
- 作为P. anaerobius的代谢物,IDA显著促进结直肠癌发生.
- IDA激活AHR,上调ALDH1A3的表达,这支持通过NADH生产抑制ferroptosis.
- 在CRC患者中,P. anaerobius被丰富,而IDA或P. anaerobius在体内促进CRC进展.
- 失去AHR或ALDH1A3会废除IDA诱导的瘤发展.
结论:
- IDA-AHR-ALDH1A3轴是铁亡相关结直肠癌的一个关键驱动因素.
- P.无氧生物的丰富和IDA的生产有助于CRC的进展.
- 针对IDA-AHR-ALDH1A3通路,为CRC提供了一个有前途的治疗策略.
更多相关视频
相关概念视频
01:29Bacterial Flora of the Large Intestine
457
The gut microbiome is formed by a vast and diverse community of bacteria that colonizes our large intestine. These bacteria start residing in the gut from birth and continue diversifying throughout life, influenced by factors such as diet, lifestyle, and stress. The gut bacterial community also includes bacteria from food and those that enter the colon through the anus.
The normal gut flora of the colon plays a critical role in generating essential vitamins such as vitamins K, B5, and B7.
The normal gut flora of the colon plays a critical role in generating essential vitamins such as vitamins K, B5, and B7.
457
01:16Necrosis
4.5K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.5K
01:15Drugs that Stabilize Microtubules
2.0K
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...
2.0K