瘤抑制剂p53的损失通过Notch信号传递对干细胞因子SOX9进行上调
bioRxiv : the preprint server for biology
|June 12, 2025
概括
瘤抑制剂p53的损失通过上调SOX9.9促进基底样乳腺癌 (BLBC) 的进展. 这通过增加Psen2表达和Notch1信号传递而发生,推动细胞脱差.
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:
- 基底类乳腺癌 (BLBC) 是三阴性乳腺癌的一种亚型,由于丰富的干状癌细胞,具有高细胞可塑性.
- 在BLBC进展过程中,光原细胞中的转录因子SOX9被上调,促进了干细胞样状态的脱差,这对恶性瘤至关重要.
- 在BLBC中驱动SOX9上调的机制在很大程度上是未知的.
研究的目的:
- 为了研究p53损失在SOX9上调中的作用,在基底类乳腺癌进展过程中.
- 阐明p53损失影响SOX9表达和蛋白质稳定性的分子机制.
主要方法:
- 利用初级乳腺细胞器官来研究p53损失的影响.
- 评估了对p53损失的反应中的SOX9表达和蛋白质半衰期.
- 研究了Psen2和Notch1信号通路的参与.
主要成果:
- 在乳腺细胞有机体中,p53的损失诱导了SOX9的表达,并稳定了其蛋白质的半衰期.
- 失去p53导致Psen2表达增加,激活Notch1信号传递.
- 激活的Notch1信号随后诱导了SOX9的表达.
结论:
- 确定了一种新的分子机制,将p53损失与BLBC中的SOX9升调联系起来.
- 证明p53的损失将SOX9与SOX9合作,推动细胞脱差异化,从而导致BLBC恶性进展.
- 这一发现突出了BLBC的潜在治疗目标.
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