在氧化应激条件下的头癌中,TM4SF19控制了GABP依赖的YAP转录
Eunbie Shin1, Yongsoo Kwon1, Eunji Jung1
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea.
烟草和酒精诱导的氧化应激通过TM4SF19促进人乳头瘤病毒阴性头支状细胞癌 (HPV- HNSCC),影响YAP转录. 准TM4SF19可能为HPV提供新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 致癌的发生是致癌的产生.
背景情况:
- 烟草和酒精是人类乳头瘤病毒阴性头支状细胞癌 (HPV- HNSCC) 的确立危险因素.
- 吸烟在HPV-HNSCC发病过程中的确切作用,尽管它具有突变性潜力和观察到的低突变负载,但仍不清楚.
- 升高的Yes相关蛋白 (YAP) mRNA是HPV-HNSCC的常见特征,独立于基因放大,升高调节的潜在机制尚不清楚.
研究的目的:
- 阐明HPV-HNSCC主要风险因素对瘤发展的贡献机制.
- 调查氧化应激和跨膜4L六家族成员19 (TM4SF19) 蛋白在调节HPV- HNSCC中的YAP转录中的作用.
- 探索针对HPV-HNSCC的TM4SF19的治疗潜力.
主要方法:
- 研究了烟草和酒精诱导的氧化应激对YAP转录的影响.
- 研究了TM4SF19在通过关氨酸和腺氨酸结合蛋白 (GABP) 复合体调解氧化应激和YAP转录之间的相互作用中的作用.
- 评估了TM4SF19枯竭对HPV- HNSCC细胞的活力,增殖和迁移的影响.
主要成果:
- 由关键风险因素引起的氧化应激通过TM4SF19.19上调调节YAP转录.
- TM4SF19与GABP转录因子复合体相互作用,在氧化应激条件下保护GABPβ1免受蛋白质体降解.
- TM4SF19的耗尽显著损害了HPV- HNSCC细胞的生存,增殖和迁移能力.
结论:
- 烟草和酒精诱导的氧化应激在HPV-HNSCC发育中发挥着关键作用,它通过TM4SF19.19促进YAP转录来促进HPV-HNSCC的发展.
- TM4SF19-GABP轴代表了一种新的机制,将环境风险因素与HPV- HNSCC中的瘤信号联系起来.
- TM4SF19成为HPV-HNSCC干预的潜在治疗标.
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