细胞内膜网膜中由压力驱动的核酸代谢促进前列腺癌的发生
Ke Deng1, Nora Pällmann2, Marte Livgård1
1Department of Biosciences, University of Oslo, Oslo, Norway; Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway.
Cancer letters
|July 5, 2025
概括
活化转录因子4 (ATF4) 和X盒结合蛋白1拼接 (XBP1s) 调节前列腺癌中的纯素代谢. 向合因子硫酶 (MOCOS) 或山丁脱酶 (XDH) 抑制癌细胞生长.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 细胞的新陈代谢
背景情况:
- 细胞内膜网膜 (ER) 压力影响癌细胞代谢和存活.
- 激活转录因子4 (ATF4) 和X盒结合蛋白1拼接 (XBP1s) 是关键的ER压力调解者.
研究的目的:
- 阐明ATF4和XBP1s在前列腺癌 (PCa) 中的纯素稳态中的作用.
- 调查向纯素代谢酶对PCa进展的影响.
主要方法:
- 在PCa细胞中研究了ATF4和XBP1s调节纯氨酸代谢酶MOCOS和XDH的作用.
- 利用基因淘汰 (MOCOS) 和基因/生化抑制 (XDH) 在体外和体内.
- 对PCa细胞增殖,殖民地形成,瘤生长,核酸平衡和DNA损伤的评估影响.
主要成果:
- 在ATF4上调节合因子硫酶 (MOCOS);XBP1s诱导脱酶 (XDH).
- MOCOS的淘汰会影响PCa细胞的增殖,殖民地形成和瘤生长.
- 抑制MOCOS会导致 purin积累,核酸失衡,复制叉停滞,以及增加DNA损伤.
- 准XDH也显著阻碍了PCa细胞的生长.
结论:
- 经ER压力介导的纯素稳态调节对于维持PCa细胞生长至关重要.
- MOCOS和XDH是这一途径的关键参与者,并代表PCa的潜在治疗点.
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