WBP1调节线粒体功能和铁亡,以调节结直肠癌中的化学抵抗
Yang Wang1, Dachuan Qi1, Guijie Ge1
1Department of General Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Molecular medicine (Cambridge, Mass.)
|March 13, 2025
概括
WW域结合蛋白1 (WBP1) 对结直肠癌 (CRC) 细胞线粒体功能和铁亡至关重要. 向WBP1使耐化学反应的CRC细胞对化疗敏感,提供了潜在的新治疗策略.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 细胞死亡机制 细胞死亡机制
背景情况:
- 耐化学反应仍然是结直肠癌 (CRC) 治疗的主要障碍,导致患者的预后不佳.
- 铁灭,一种受调节的细胞死亡形式,正在成为影响各种癌症化学抵抗的潜在因素.
研究的目的:
- 研究WW域结合蛋白1 (WBP1) 在调节线粒体功能,细胞生长,铁亡以及结直肠癌 (CRC) 细胞中的化学抵抗中的作用.
- 确定是否准WBP1或与之相关的线粒体通路可以克服CRC中的化学抵抗.
主要方法:
- 在CRC细胞模型中利用了遗传 (WBP1枯竭) 和药理学方法.
- 评估了线粒体呼吸,细胞增殖和铁灭诱导.
- 使用外源性线粒体恢复线粒体功能.
- 分析了患者转录组数据,以将WBP1表达与临床结果相关联.
主要成果:
- 在CRC细胞中,WBP1对于维持线粒体呼吸至关重要.
- 缺少WBP1会损害线粒体功能,减少细胞增殖,增加铁亡.
- 在WBP1缺乏的细胞中恢复线粒体功能,使增殖正常化,并抑制铁亡.
- 向WBP1或线粒体功能通过ferroptosis诱导使耐化学反应的CRC细胞对5-fluorouracil和oxaliplatin敏感.
- 在CRC患者中增加WBP1表达与化疗接受者中较差的结果相关.
结论:
- 在结直肠癌 (CRC) 细胞中,WBP1显著调节线粒体功能和铁亡.
- 准WBP1是一个有前途的治疗策略,用于对抗CRC的化学抵抗.
- 这些发现提高了对CRC化学抵抗机制的理解,并可能为新疗法开发提供信息.
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