通过mTOR对HOXB13的层次酸化决定了其在前列腺癌中的活性和瘤功能
Yonghong Chen1,2, Catherine R Dufour1, Lingwei Han1,2
1Goodman Cancer Institute, McGill University, Montréal, Québec, Canada.
Molecular cancer research : MCR
|July 6, 2023
概括
哺乳动物的目标拉巴胺素 (mTOR) 直接化HOXB13,增强其致癌性质并促进前列腺癌的生长. 这种酸化会产生独特的基因特征,有助于区分前列腺癌的不同阶段.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 拉巴胺素 (mTOR) 信号传导的哺乳动物目标失调是前列腺癌进展的关键驱动因素.
- 转录因子HOXB13影响雄激素反应和前列腺癌的发展.
- 最近的一项发现表明,HOXB13与mTOR在染色质上形成复合体,这表明存在功能联系.
研究的目的:
- 为了阐明前列腺癌中HOXB13和mTOR之间的功能交叉.
- 研究mTOR如何影响HOXB13活性和瘤潜在的机制.
主要方法:
- 通过mTOR.研究了HOXB13的直接相互作用和等级酸化.
- 利用相仿性突变来评估酸化的功能影响.
- 进行了体外和体内 (小鼠外移植) 研究,以评估前列腺癌细胞生长.
- 进行了转录分析,以确定HOXB13依赖基因特征.
主要成果:
- mTOR在特定的部位 (Thr8,Thr41,Ser31) 直接酸化HOXB13.
- 酸化促进HOXB13与E3结合酶SKP2的相互作用,增强其致癌性质.
- 突变HOXB13具有相仿突变,在体外和体内加速前列腺癌的生长.
- 一个依赖-HOXB13的基因特征有效地区分了正常,原发性和转移性前列腺癌组织.
结论:
- mTOR直接酸化HOXB13,建立一个驱动前列腺癌的分子级联.
- -HOXB13决定了一个特定的基因程序,具有显著的致癌影响.
- 通过mTOR向HOXB13酸化代表了晚期前列腺癌的潜在治疗策略.
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