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CDCA8通过稳定低氧条件下的HIF1α表达来促进膀癌的生存

Qiang Zhou^1,2, Wei Huang¹, Jing Xiong^1,2

¹Department of Urology, First Affiliated Hospital of Nanchang University, Nanchang, China.

Cell death & disease

|October 9, 2023

概括

细胞周期基因CDCA8通过AKT通路稳定HIF1α,促进低氧下膀癌的生存. 上调的CDCA8与晚期疾病和低生存率相关,将其确定为潜在的治疗标.

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:

缺氧是固体瘤的一个关键特征,驱动瘤细胞的适应和生存.
缺氧诱导因子1-α (HIF1α) 是细胞对低氧环境反应的关键调节者.
膀癌 (BCa) 的进展通常与缺氧状况有关.

研究的目的:

在低氧条件下研究细胞周期分裂相关基因8 (CDCA8) 在膀癌细胞中的作用.
阐明CDCA8通过哪些分子机制影响BCa细胞在缺氧中的生存.
评估CDCA8作为膀癌的潜在治疗点.

主要方法:

在BCa细胞系和临床样本中分析CDCA8表达.
在低氧条件下评估CDCA8对BCa细胞存活的要求.
研究CDCA8,HIF1α,PTEN和AKT信号传输之间的相互作用.
路西法酶记者测定证实了HIF1α介导的CDCA8.8的转录激活.

主要成果:

在BCa细胞系和临床样本中,CDCA8显著上调,与晚期,等级和整体存活率 (OS) 差异相关.
在低氧环境中,CDCA8蛋白表达对BCa细胞生存至关重要.
CDCA8通过与PTEN竞争AKT结合来稳定HIF1α,从而导致PTEN移位和AKT/GSK3β通路的激活.
HIF1α直接与CDCA8促进体结合,创建一个积极反循环,增强HIF1α的稳定性.

结论:

CDCA8在使膀癌细胞适应和生存缺氧方面发挥着至关重要的作用.
CDCA8-HIF1α正反循环对于在低氧瘤微环境中维持膀癌细胞至关重要.
CDCA8代表了膀癌治疗的新且有前途的治疗标.

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