Silencing Notch4 promotes tumorigenesis and inhibits metastasis of triple-negative breast cancer via Nanog and Cdc42

Autor: Yuan Tian, Peipei Zhang, Yajun Mou, Wenxiu Yang, Junhong Zhang, Qing Li, Xiaowei Dou
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Death Discovery, Vol 9, Iss 1, Pp 1-10 (2023)
Druh dokumentu: article
ISSN: 2058-7716
DOI: 10.1038/s41420-023-01450-w
Popis: Abstract 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.
Databáze: Directory of Open Access Journals