葡萄糖皮质醇受体诱导的非肌肉调节了割抵抗性前列腺癌的转移
Verneri Virtanen1, Kreetta Paunu1, Antti Kukkula1
1Cancer Research Unit, Institute of Biomedicine, and FICAN West Cancer Center Laboratory, University of Turku, and Turku University Hospital, Kiinamyllynkatu 10, 20520, Turku, Finland.
Oncogenesis
|August 12, 2023
概括
葡萄糖皮质体受体 (GR) 在前列腺癌 (PCa) 中高调低分子量卡尔德斯蒙 (l-CaD). 这种GR调节的l-CaD促进PCa转移,特别是在对抗雄激素疗法产生耐药性时.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 细胞生物学 细胞生物学
背景情况:
- 致死性前列腺癌 (PCa) 是由转移和耐治疗性标志着.
- 细胞骨重塑,特别是涉及到actin,对于转移形成至关重要.
- CALD1基因编码卡尔德斯蒙 (CaD),低分子量异型 (l-CaD) 调节非肌肉细胞中的细胞骨动力学.
研究的目的:
- 为了研究前列腺癌中l-CaD的调节.
- 确定l-CaD在PCa转移和治疗耐药性的作用.
- 探索PCa中葡萄糖皮质体受体 (GR) 和l-CaD之间的关系.
主要方法:
- 在体外研究涉及l-CaD下调和GR激活.
- 3D球形生长测试.
- 在体内斑马鱼PCa异种移植模型.
- 对CALD1和GR表达相关性PCa患者数据的分析.
- 对抗雄激素治疗耐药的PCa异种移植小鼠模型中的l-CaD表达的评估.
主要成果:
- 降低l-CaD的调节减少了PCa球状体在体外生长和体内转移.
- 在PCa患者中,CALD1mRNA表达与表皮细胞转移到介质细胞转移 (EMT) 标记相关.
- 在PCa数据集中,CALD1和GR具有很高的共同表达,GR激活可以调节l-CaD.
- 在抗雄激素治疗耐药的PCa模型中,GR上调导致l-CaD表达的增加.
结论:
- GR调节的l-CaD在前列腺癌转移中起着重要作用.
- GR-l-CaD轴在PCa中具有临床意义,该PCa通过GR上调来发展抗雄激素治疗的耐药性.
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