ZHX2缺乏通过调节E-cadherin表达来丰富混合MET细胞
Yan He1, Qimin Zhang1, Yuanhong Chen1
1National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Cell death & disease
|July 17, 2023
概括
丧失ZHX2促进了三阴性乳腺癌 (TNBC) 细胞中的混合上皮层-介质细胞转换 (MET) 状态. 这种转变通过重新激活E-cadherin表达来损害癌症的进展和肺转移.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 皮质到介质细胞 (E/M) 杂交状态与瘤发生有关.
- 在体内观察到一种混合介质到上皮细胞过渡 (MET) 状态,其特征是表皮细胞和介质细胞标记物的共同表达,并且与癌症进展有关.
- 在三阴性乳腺癌 (TNBC) 细胞中维持混合MET状态的确切作用和分子机制尚未完全理解.
研究的目的:
- 调查ZHX2在TNBC中维持混合MET状态中的作用.
- 阐明ZHX2影响混合MET表型的分子机制.
- 确定ZHX2损失在TNBC进展和转移中的功能和临床影响.
主要方法:
- 在中细胞TNBC细胞中ZHX2耗尽.
- 对CDH1促进剂活性和E-cadherin表达的分析.
- 在临床前模型中评估细胞迁移,有机体扩散和肺转移的功能性测试.
- 在TNBC患者样本中对ZHX2和E-cadherin表达的相关性分析.
主要成果:
- 丧失ZHX2表达会诱导介质TNBC细胞中的混合MET表型.
- ZHX2 枯竭通过直接与 CDH1 促进体结合来重新激活 E-cadherin 表达.
- 丧失ZHX2抑制TNBC细胞迁移和传播,抑制肺转移,这种效应可以通过恢复E-cadherin来逆转.
- 在人类TNBC患者中,ZHX2被放大并与E-cadherin表达负相关.
结论:
- 丢失ZHX2通过重新激活E-cadherin促进TNBC中的混合MET状态.
- 这种ZHX2-介导的混合MET状态会损害TNBC细胞的迁移,传播和转移.
- ZHX2代表了管理TNBC进展的潜在治疗标.
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