线粒体展开的蛋白质响应依赖β-catenin信号传递促进神经内分泌前列腺癌
Jordan Alyse Woytash1, Rahul Kumar1, Ajay K Chaudhary1
1Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA.
Oncogene
|December 17, 2024
概括
线粒体展开蛋白反应 (UPRmt) 通过增强线粒体功能和抗西斯普拉丁耐药性来促进侵袭性神经内分泌前列腺癌 (NEPC). 抑制UPRmt,特别是HSP60,为这种致命的癌症提供了一个有希望的治疗策略.
科学领域:
- 线粒体生物学 线粒体生物学
- 癌症生物学 癌症生物学
- 前列腺癌研究 研究前列腺癌研究
背景情况:
- 线粒体展开蛋白质反应 (UPR) 对于线粒体质量控制至关重要.
- 它在侵袭性和抗性前列腺癌,特别是割抗性神经内分泌前列腺癌 (CRPC-NE) 中的作用尚不清楚.
- 尽管存在补偿性UPRmt上调,但CRPC-NE瘤表现出功能障碍的氧化酸化 (OXPHOS).
研究的目的:
- 调查UPR在CRPC-NE.中扮演的角色.
- 在NEPC中探索UPRmt作为潜在的治疗点.
主要方法:
- 对CRPC-NE瘤的生物化学和蛋白质分析.
- 热冲击蛋白60 (HSP60) 的遗传删除和药理抑制.
- 评估β-catenin信号传递和线粒体生物能量学.
主要成果:
- 在CRPC-NE瘤中,UPRmt和核编码的OXPHOS蛋白质呈上调.
- 抑制HSP60减少了NEPC的生长,并使细胞恢复到类似上皮质的状态.
- UPRmt通过β-catenin信号传递促进OXPHOS和线粒体的生物能量,有助于对西斯普拉丁的抗性.
- 抑制UPRmt抑制了侵略性的NEPC表型和转移潜力.
结论:
- UPR通过β-catenin信号传递促进线粒体健康和积极的NEPC表型.
- 在CRPC-NE中,UPR与线粒体生物发生和 Cisplatin 耐药性有关.
- 针对UPRmt,特别是HSP60,是NEPC的一种可行的治疗策略.
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