纤维素1通过Akt/CREB信号通路调节RAP1B蛋白稳定性,加剧结肠癌转移
Zhonghe Ji1, Xinbao Li2, Yadong Wang3
1Department of Peritoneal Oncology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
Journal of cellular and molecular medicine
|July 10, 2025
概括
纤维素1 (FN1) 通过增强细胞迁移和入侵来驱动结肠癌转移. 这种蛋白质可以作为预防癌症扩散的治疗点.
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:
- 转移显著恶化结肠癌的预后,但其潜在的分子机制尚不清楚.
- 识别结肠癌转移的关键驱动因素对于开发有效的治疗策略至关重要.
研究的目的:
- 阐明纤维素1 (FN1) 促进结肠癌转移的分子机制.
- 研究FN1在结肠癌细胞行为中的作用及其作为治疗点的潜力.
主要方法:
- RNA测序 (RNA-seq) 用于识别转移性结肠癌中差异表达的基因.
- 在体外测试以评估细胞迁移,入侵和上皮-介质细胞过渡 (EMT).
- 在裸体小鼠中的体内转移模型和涉及蛋白质-蛋白质相互作用和信号通路 (Akt,CREB) 的分子机制研究.
主要成果:
- 纤维素1 (FN1) 在转移性结肠癌中显著上调,并与预后不佳有关.
- 在体外,FN1通过RAP1B促进了结肠癌细胞迁移,入侵和EMT,并在体内通过RAP1B促进了肝/肺转移.
- FN1通过抑制其无处不在的作用稳定了RAP1B,激活了Akt/CREB通路,并建立了一个积极的反循环,涉及CREB介导的FN1和TIMP1.1的转录.
结论:
- 在促进结肠癌迁移,入侵和转移方面,FN1发挥着至关重要的作用.
- FN1-RAP1B-Akt-CREB信号轴是推动结肠癌进展的关键机制.
- FN1代表了抑制结肠癌转移的潜在治疗标.
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