剩余的乳腺癌细胞共同选择SOX5驱动的内分体骨化来维持休眠状态
Amulya Sreekumar1,2, Eric Blankemeyer3, Christopher J Sterner1,2
1Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, PA 19104, USA.
bioRxiv : the preprint server for biology
|July 14, 2025
概括
转录因子SOX5/6调节乳腺癌复发. SOX5通过诱导内分体骨化促进休眠状态,防止癌症复发并改善存活率.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 复发性乳腺癌是癌症死亡的主要原因.
- 治疗耐药的残留瘤细胞 (RTC) 和复发的机制尚不清楚.
研究的目的:
- 为了确定乳腺癌复发和休眠期的分子调节者.
- 研究SOX5/6转录因子在RTC休眠和复发中的作用.
主要方法:
- 使用CRISPR-Cas9查来确定瘤复发的调节者.
- 使用NaF-PET成像来确认内分泌骨化.
- 对患者样本进行基因表达分析.
主要成果:
- 失去SOX5加速了乳腺癌复发和休眠状态的逃脱.
- 在休眠的RTC中,SOX5诱导了一种依赖于软骨的骨发育程序 (内分泌骨化).
- 患者的骨质突变基因表达预测了改善的无复发生存率.
结论:
- 依赖SOX5的间皮转分化是一种预防乳腺癌复发的适应机制.
- 通过SOX5加强瘤细胞休眠可能是预防复发的治疗策略.
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