蛋白SET相关转录因子ZBTB11触发肺癌转移
Wenbin Xu1, Han Yao1, Zhen Wu1
1State Key Laboratory of Common Mechanism Research for Major Diseases & Department of Medical Genetics, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China.
Nature communications
|February 15, 2024
概括
指和BTB域含有蛋白11 (ZBTB11) 通过激活矩阵金属蛋白酶-9和富含proline的Gla蛋白来驱动肺癌转移. 丧失ZBTB11抑制转移,突出其作为关键调节者的作用.
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:
- 转移是肺癌死亡的主要原因,其潜在机制需要进一步阐明.
- SE转位 (SET) 在肺瘤中过度表达,并与预后不佳有关.
研究的目的:
- 在肺瘤中识别和表征新型前列腺转移调节剂.
- 阐明ZBTB11促进肺癌转移的机制.
主要方法:
- 共同免疫沉和西部斑点测试,以评估蛋白质相互作用.
- 定量实时PCR和西式涂抹分析基因和蛋白质表达.
- 在体外细胞迁移和入侵测定.
- 在体内肺瘤转移的小鼠模型.
主要成果:
- ZBTB11被确定为一种与SET相关的转录因子,促进肺癌细胞迁移和入侵.
- 该SET-ZBTB11复合体激活矩阵金属蛋白酶-9 (MMP9) 转录,增强转移.
- ZBTB11独立地抑制了富含林的Gla蛋白2 (PRRG2) 转录,与Yes相关蛋白1 (YAP1) 激活和转移联系在一起.
- 在体内,ZBTB11敲击抑制了远端肺瘤转移.
- 人类转移性肺瘤中ZBTB11过度表达与患者存活时间减少相关.
结论:
- 通过多种机制,ZBTB11是肺瘤转移的关键调节者.
- 向ZBTB11可能提供一种抑制肺癌传播的治疗策略.
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