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在人类乳腺上皮细胞中,CDH1损失重塑基因表达和血统身份
Maggie Musick1, Chinasa A Ufondu2, Carmen E Rowland1
1Department of Pathology, University of Colorado Anschutz Medical Campus.
bioRxiv : the preprint server for biology
|July 16, 2025
概括
侵袭性叶状癌 (ILC) 中的CDH1遗传损失将细胞重新编程为类似光原体的状态,与激发EMT的抗体诱导的E-cadherin抑制不同. 这种早期的CDH1损失增强了增殖,在瘤启动方面提供了克隆优势.
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:
- 侵袭性叶膜癌 (ILC) 的特点是CDH1损失,影响E-cadherin功能.
- 在早期的ILC瘤发生过程中,CDH1/E-cadherin的瘤抑制机制尚未完全理解.
研究的目的:
- 调查早期CDH1损失如何影响ILC瘤发生.
- 为了区分细胞对E-cadherin抑制的反应与遗传CDH1损失.
主要方法:
- 利用人类乳腺上皮细胞 (HMEC) 模型来准CDH1/E-cadherin.
- 采用抗体抑制,siRNA,CRISPR/Cas9用于CDH1损失,转录组分析,单细胞转录组学和流细胞计.
主要成果:
- 抗体介导的E-cadherin抑制诱导的上皮层-介质细胞过渡 (EMT) 签名.
- 遗传CDH1损失抑制了EMT,并将基因表达转向光表皮表型.
- CDH1损失将细胞重新编程到类似光原体的状态,增强增殖能力.
结论:
- 失去了E-cadherin的方法批判性地决定了细胞表型.
- 在ILC瘤发生过程中遗传的CDH1损失促进了光线前类状态,有助于瘤的启动.
- 这些发现为推动ILC发展的早期事件提供了新的见解.
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