下调的CCND3是在获得的西斯普拉丁耐药性期间驱动肺腺癌转移的一个关键事件
Yun Su1, Yuting Ma1, Yubing Wang2
1Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Guangzhou Medical University, Guangzhou 511436, China.
International journal of biological sciences
|January 9, 2025
概括
循环D3 (CCND3) 损失意外地促进了肺腺癌 (LUAD) 转移和通过改变细胞骨架重塑和上皮-介质酶过渡 (EMT) 来改变 Cisplatin 耐药性. 这种CCND3下调与患者生存率差有关.
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:
- 已知循环D3 (CCND3) 能调节细胞循环的进展.
- 对西斯丁 (DDP) 的获得性耐药性是治疗肺腺癌 (LUAD) 的一个主要挑战.
研究的目的:
- 研究CCND3在cisplatin耐药性和LUAD转移中的作用.
- 阐明将CCND3与化学抵抗和瘤进展联系起来的潜在分子机制.
主要方法:
- 在抗DDP的LUAD细胞和临床样本中分析CCND3表达.
- 在体内和体外研究,以评估CCND3下调对转移的影响.
- 研究参与CCND3调节和功能的信号通路 (PI3K/Akt/c-Jun) 和蛋白相互作用 (PARK2,维丁).
主要成果:
- 在抗DDP的LUAD细胞中,CCND3的下调,阻碍了细胞周期过渡.
- CCND3损失引发了细胞骨重塑,化学抵抗,并加速了LUAD转移.
- 在CCND3表达和淋巴转移/患者存活率之间观察到负相关性.
- 从机制上讲,PI3K/Akt/c-Jun信号抑制了CCND3转录,减少了通过PARK2降解维门丁,并促进了EMT.
结论:
- 降低CCND3的调节在促进LUAD进展和获得的西斯普拉丁耐药性方面发挥着至关重要的作用.
- PI3K/Akt/c-Jun/CCND3/PARK2/vimentin轴是驱动DDP抗性LUAD中EMT,转移和化学抵抗的关键途径.
- 针对CCND3或其相关途径可能提供治疗策略,以克服LUAD中西斯普拉丁耐药性.
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