HIF-1α knockdown suppresses breast cancer metastasis via epithelial mesenchymal transition Abrogation
Jinjin Zhao,
Haiguang Zhang,
Yaqian Liu,
Guangjian Lu,
Zhaohui Wang,
Qingjiang Mo,
Guoqiang Wang,
Yanfei Shen,
Luyang Jiao
Affiliations
Jinjin Zhao
Clinical Laboratory, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China; Life Science Research Center, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China
Haiguang Zhang
Department of Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China
Yaqian Liu
Otorhinolaryngology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China; Life Science Research Center, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China
Guangjian Lu
Clinical Laboratory, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China
Zhaohui Wang
Clinical Laboratory, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China
Qingjiang Mo
Clinical Laboratory, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China
Guoqiang Wang
Clinical Laboratory, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China
Yanfei Shen
Clinical Laboratory, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China; Medical School, Southeast University, Nanjing, Jiangsu, 210009, China; Corresponding author. Clinical Laboratory, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China.
Luyang Jiao
Clinical Laboratory, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China; Department of Blood Transfusion, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453100, China; Corresponding author. Clinical Laboratory, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453100, China.
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.
