ROCK1通过PRKCH介导的生物能量重编程驱动结直肠癌肝脏转移
Yue Luo1, Yishan Xu2, Xi Chen2
1Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325035, PR China; Wenzhou Key Laboratory of Integrated Traditional Chinese and Western Medicine Treatment for Gastrointestinal Diseases, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325035, PR China.
Cellular signalling
|October 20, 2025
概括
这项研究揭示了与Rho相关的coil-coil激酶1 (ROCK1) 驱动着结直肠癌 (CRC) 通过调节表皮-介质细胞转变和新陈代谢来驱动肝转移. 蛋白激酶C eta (PRKCH) 被确定为该途径的关键下游目标.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症转移研究 癌症转移研究
背景情况:
- 结肠直肠癌 (CRC) 肝脏转移是癌症死亡的主要原因.
- 驱动CRC转移的分子机制尚未完全理解.
研究的目的:
- 为了确定结直肠癌肝脏转移的关键分子调节剂.
- 阐明参与CRC转移进展的信号通路.
主要方法:
- 对患者瘤样本进行ROCK1表达的分析.
- 在体外和体外功能测定评估ROCK1和PRKCH在CRC细胞迁移和殖民中的作用.
- 转录形状分析以识别下游影响者.
- 路西法酶记者测定验证转录因子结合.
主要成果:
- 在肝转移中,ROCK1表达升高,并促进CRC细胞迁移和肝脏殖民.
- ROCK1调节表皮层-介质酶过渡 (EMT) 标记物,并控制PRKCH的表达.
- PRKCH沉默会损害CRC细胞运动性和代谢功能;其过度表达会挽救这些缺陷.
- 在ERK2-CREB1信号轴中介于ROCK1驱动的PRKCH转录.
结论:
- 一个新的ROCK1-ERK2-CREB1-PRKCH信号通路通过协调EMT和代谢重编程来驱动CRC肝转移.
- 对于晚期结直肠癌,PRKCH 是一个潜在的治疗点.
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