通过激活HSP90α/CDK6/β-catenin轴,通过瘤干的介导,GART促进多发性骨髓瘤恶性
Jinjun Qian1, Han Meng2, Ze Wang2
1Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210022, China; School of Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
European journal of pharmacology
|April 4, 2025
概括
甘氨酸胺核酸转化酶 (GART) 通过稳定HSP90α和激活Wnt/β-catenin通路来驱动多发性骨髓瘤 (MM) 细胞生长和干细胞. 用pemetrexed准GART显示了MM治疗的希望.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症干细胞研究研究
背景情况:
- 瘤进展与类似干细胞的特征有关.
- 甘胺核酸转化酶 (GART) 涉及固体瘤干,但其在多发性骨髓瘤 (MM) 中的作用尚不清楚.
研究的目的:
- 研究GART对MM细胞增殖和干细胞的影响.
- 评估GART作为MM的潜在治疗标.
主要方法:
- 在体外研究:GART过度表达和MM细胞的敲击.
- 在体内研究:小鼠模型 (化学诱导的血细胞瘤和CDX模型).
- 机制研究:研究GART与HSP90α,CDK6和Wnt/β-catenin通路的相互作用.
主要成果:
- 升高的GART与MM干性标志物和患者的不良结果相关.
- GART促进了MM细胞的增殖,殖民地形成和细胞周期的进展.
- GART稳定了HSP90α,上调了CDK6,并激活了Wnt/β-catenin通路,增强了茎状.
- 使用pemetrexed抑制了MM细胞的增殖和瘤生长的GART抑制 in vivo.
结论:
- GART通过HSP90α/CDK6/β-catenin轴促进MM细胞的增殖和干细胞.
- 向GART代表了对多发性髓瘤的潜在治疗策略.
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