激活转录因子5促进神经母细胞瘤转移,通过诱导阿诺基斯的抵抗
Debarshi Banerjee1, Shuobo Boboila1,2, Shunpei Okochi3
1Department of Pediatrics, Columbia University Irving Medical Center, New York, New York.
Cancer research communications
|November 28, 2023
概括
激活转录因子5 (ATF5) 驱动神经母细胞瘤转移,通过防止细胞死亡或细胞死亡. 用CP-d/n-ATF5向ATF5可能会抑制高风险神经母细胞瘤患者的转移.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症转移 癌症转移
背景情况:
- MYCN增强神经母细胞瘤具有攻击性,预后不佳.
- 激活转录因子5 (ATF5) 与神经分化和癌症存活率有关.
- 高ATF5表达与第四阶段高风险神经母细胞瘤的预后不佳相关.
研究的目的:
- 研究ATF5在神经母细胞瘤转移中的作用.
- 阐明ATF5促进转移的机制.
- 评估针对ATF5.5的治疗潜力.
主要方法:
- 在神经母细胞瘤患者样本中评估ATF5表达.
- 在体内使用异种移植模型来研究ATF5对瘤生长和转移的作用.
- 研究了ATF5在阿诺基基抗性中的作用及其对BMF的调节.
- 测试了一种主导负ATF5 (CP-d/n-ATF5) 对抗转移效应.
主要成果:
- 在高风险神经母细胞瘤中ATF5的表达很高,并且与预后较差有关.
- 在体内,ATF5促进神经母细胞瘤细胞转移,减少异种移植瘤的生长和扩散到骨髓和肝脏.
- 通过转录性抑制BMF,ATF5赋予了对anoikis的抵抗力,提高了循环瘤细胞的存活率.
- CP-d/n-ATF5治疗抑制了神经母细胞瘤的转移,并诱导了的敏感性.
结论:
- ATF5 是神经母细胞瘤转移的关键促进体.
- 在神经母细胞瘤中,ATF5调解了阿诺基斯的抗性.
- 用CP-d/n-ATF5向ATF5是对转移性神经母细胞瘤的一种有前途的治疗策略.
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