雄激素受体通过与胃癌中的YAP1辅因子相互作用,促进细胞干细胞的形成
Junyi Hou1, Tao Pan1, Fangyuan Li1
1Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
Biochemical pharmacology
|October 8, 2023
概括
雄激素受体 (AR) 促进癌症干细胞 (CSC) 的特征和胃癌中的化学抵抗. 向AR及其辅因子YAP1为胃癌患者提供了潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 癌症干细胞 (CSCs) 与瘤复发和化学抵抗有关.
- 雄激素受体 (AR) 是各种癌症中干性的潜在调节者.
- 胃癌 (GC) 干细胞和化学抵抗中AR的作用尚不清楚.
研究的目的:
- 阐明AR调节的CSC特性和胃癌中化学抵抗的机制.
- 调查AR表达与患者存活率和GC中CSC表型之间的相关性.
- 根据AR信号来确定GC的潜在治疗点.
主要方法:
- 在GC组织中分析AR表达和与患者存活率和CSC标记物的相关性.
- 在体外实验中评估AR过度表达和抑制对GC细胞干细胞 (瘤球体形成) 和化学抵抗的影响.
- 使用异种移植模型进行体内研究,以评估AR对胃瘤发生和化学敏感性的影响.
- 机理研究涉及AR促进体结合试验和共免疫沉,以评估YAP1作为辅助因子的作用.
主要成果:
- 在GC组织中,AR是上调调节的,与低生存率和CSC表型相关.
- 过度表达的AR增强了CSC标记物的表达,瘤球体的形成,以及GC细胞中的化学抵抗.
- 抑制AR减弱了这些茎状性质,并增加了化学敏感性.
- 通过与其促进体结合,AR直接调节CD44的表达,YAP1作为辅助因子.
结论:
- 在胃癌中,AR通过调节CD44表达,部分通过其与YAP1的相互作用来促进CSC特性和化学抵抗.
- 抗逆转录蛋白信号传递是克服化疗抵抗和改善胃癌患者治疗结果的潜在治疗标.
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