HIF-1α knockdown suppresses breast cancer metastasis via epithelial mesenchymal transition Abrogation

Autor: Jinjin Zhao, Haiguang Zhang, Yaqian Liu, Guangjian Lu, Zhaohui Wang, Qingjiang Mo, Guoqiang Wang, Yanfei Shen, Luyang Jiao
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Heliyon, Vol 10, Iss 19, Pp e37900- (2024)
Druh dokumentu: article
ISSN: 2405-8440
DOI: 10.1016/j.heliyon.2024.e37900
Popis: Lung metastasis, a leading cause of breast cancer mortality, lacks effective therapeutic options. Hypoxia-inducible factor 1-alpha (HIF-1α) plays important roles in breast cancer progression, but its direct impact on lung metastasis remains unclear. Herein, in this study, we investigated the role of HIF-1α in breast cancer lung metastasis and the potential of targeting it for therapeutic benefit. HIF-1α expression was knocked down in the 4T1 mouse mammary carcinoma cell line using a lentiviral vector. HIF-1α knockdown significantly reduced the migratory ability of 4T1 cells in vitro and lung metastasis in a mouse model. Mechanistically, HIF-1α knockdown decreased the expression of matrix metalloproteinases (MMP-2 and MMP-9) that degrade the extracellular matrix and suppressed the epithelial-to-mesenchymal transition (EMT) by increasing E-cadherin and decreasing vimentin expression. The findings of this study demonstrate that HIF-1α knockdown effectively inhibits lung metastasis of 4T1 cells both in vitro and in vivo by suppressing EMT. These results underscore a promising new approach for managing breast cancer metastasis.
Databáze: Directory of Open Access Journals