XAF1通过VCP-RNF114-JUP轴促进结直肠癌的转移
1CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences , Shanghai, China.
The Journal of cell biology
|December 14, 2023
概括
与XIAP相关的亡抑制因子1 (XAF1) 促进结直肠癌 (CRC) 转移,通过调节结合球蛋白 (JUP) 降解. 针对XAF1-VCP-RNF114-JUP通路可能提供新的CRC治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 转移是结直肠癌 (CRC) 死亡的主要原因,远程转移病例的5年生存率仅为14%.
- 干扰素诱导的蛋白质X关联亡抑制剂 (XIAP) 相关因子1 (XAF1) 已涉及到各种细胞过程.
研究的目的:
- 为了研究XAF1在结肠直肠癌 (CRC) 转移中的作用.
- 阐明XAF1影响CRC细胞迁移和转移的分子机制.
主要方法:
- 研究了XAF1作为一种适应蛋白质,用于含有瓦洛的蛋白质 (VCP).
- 检查了XAF1对RING指蛋白114 (RNF114) 中介于VCP的二维基因化的影响.
- 评估了对结位球蛋白 (JUP) 无化和降解的影响.
- 在临床CRC样本中,XAF1,RNF114和JUP的相关蛋白质水平.
主要成果:
- XAF1充当了VCP的新型适配器,促进了VCP介导的RNF114.4的脱化.
- 这种相互作用促进了与K48相关的泛化和JUP的后续降解.
- 已识别的XAF1-VCP-RNF114-JUP通路对于CRC细胞迁移和转移至关重要.
- 临床样本显示了XAF1,RNF114和JUP蛋白水平之间的相关性.
结论:
- 通过促进转移,XAF1在转移性结直肠癌 (mCRC) 中起着显著的致癌作用.
- XAF1-VCP-RNF114-JUP信号轴代表了CRC治疗的潜在治疗目标.
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