前列腺癌利用BRD9驱动的代谢重编程来塑造侵略性的表型
Ye Lv1, Xinkai Mo2, Ruojia Zhang3
1Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, Shandong, China.
含有基多马因的蛋白9 (BRD9) 有助于侵袭性前列腺癌 (PCa) 细胞在割抵抗期间适应氧化应激. 抑制BRD9会破坏这种平衡,使PCa细胞对放射治疗更加敏感.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症新陈代谢 癌症新陈代谢
背景情况:
- 前列腺癌 (PCa) 进展为抗割PCa (CRPC) 涉及适应雄激素缺乏 (AD) 和氧化应激.
- 在CRPC期间能够维持氧化还原平衡的特定瘤基因仍然不完全理解.
研究的目的:
- 为了确定关键的瘤基因参与维护在CRPC期间的氧化还原平衡.
- 调查含odomain蛋白9 (BRD9) 在代谢重编程和压力下割抵抗中的作用.
主要方法:
- 确定BRD9作为代谢检查点.
- 分析BRD9对核转录因子-Y A亚单元 (NFYA) 的招募和诱导糖原酶L (PYGL) 表达的分析.
- 评估BRD9抑制对PCa细胞中氧化还原稳态和放射敏感性的影响.
主要成果:
- BRD9充当代谢检查点,重编程细胞代谢以支持瘤生长和割抵抗.
- 在氧化后,BRD9招募NFYA来上调PYGL,将葡萄糖引导到酸通路,用于NADPH生成和反应性氧物种 (ROS) 清除.
- 抑制BRD9会破坏氧化还原稳定,增加氧化压力,使PCa细胞对放射治疗敏感.
结论:
- BRD9是抗氧化剂重编程的新型成分,对CRPC进展至关重要.
- 向BRD9代表了增强前列腺癌治疗的有希望的治疗策略,特别是与放射治疗结合使用.
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