Tian Yuan, Zhang Peipei, Mou Yajun, Yang Wenxiu, Zhang Junhong, Li Qing, Dou Xiaowei
Department of Pathology, The Affiliated Hospital of Guizhou Medical University, 550004, Guiyang, Guizhou, China.
Clinical Research Center, The Affiliated Hospital of Guizhou Medical University, 550004, Guiyang, Guizhou, China.
Cell Death Discov. 2023 May 6;9(1):148. doi: 10.1038/s41420-023-01450-w.
Elucidation of individual Notch protein biology in specific cancer is crucial to develop safe, effective, and tumor-selective Notch-targeting therapeutic reagents for clinical use [1]. Here, we explored the Notch4 function in triple-negative breast cancer (TNBC). We found that silencing Notch4 enhanced tumorigenic ability in TNBC cells via upregulating Nanog expression, a pluripotency factor of embryonic stem cells. Intriguingly, silencing Notch4 in TNBC cells suppressed metastasis via downregulating Cdc42 expression, a key molecular for cell polarity formation. Notably, downregulation of Cdc42 expression affected Vimentin distribution, but not Vimentin expression to inhibit EMT shift. Collectively, our results show that silencing Notch4 enhances tumorigenesis and inhibits metastasis in TNBC, indicating that targeting Notch4 may not be a potential strategy for drug discovery in TNBC.
阐明特定癌症中单个Notch蛋白的生物学特性对于开发安全、有效且具有肿瘤选择性的Notch靶向治疗试剂以供临床使用至关重要[1]。在此，我们探究了Notch4在三阴性乳腺癌（TNBC）中的功能。我们发现，沉默Notch4通过上调Nanog（一种胚胎干细胞多能性因子）的表达增强了TNBC细胞的致瘤能力。有趣的是，在TNBC细胞中沉默Notch4通过下调Cdc42（细胞极性形成的关键分子）的表达抑制了转移。值得注意的是，Cdc42表达的下调影响波形蛋白的分布，但不影响波形蛋白的表达以抑制上皮-间质转化（EMT）转变。总体而言，我们的结果表明，沉默Notch4增强了TNBC的肿瘤发生并抑制了转移，这表明靶向Notch4可能不是TNBC药物研发的潜在策略。
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