Krüppel-like factor 4 modulates the migration and invasion of hepatoma cells by suppressing TIMP-1 and TIMP-2

Ming T.A. Sung, Hui Tzu Hsu, Chih Chun Lee, Hsin Chen Lee, Ying J.U. Kuo, Kate Hua, Cheng Yuan Hsia*, Chin Wen Chi

*此作品的通信作者

研究成果: Article同行評審

17 引文 斯高帕斯(Scopus)

摘要

Krüppel-like factor 4 (KLF4) plays important roles in development, stemness and tumorigenesis; however limited information is available on the detailed function of KLF4 in hepatocellular carcinoma (HCC). The objective of the present study was to examine the functional roles of KLF4 in the metastasis of HCC cells. KLF4 was overexpressed and knocked down by lentiviral transduction method in highly metastatic HCC cells. KLF4 overexpression in HCC cells led to inhibition of cell migration and invasion. These inhibitory effects were associated with the upregulation of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 by KLF4. Treatment with recombinant TIMP-1 decreased the migratory ability of HCC cells. Moreover, myeloperoxidase (MPO)-TIMP-1/TIMP-2 inactivator counteracted the KLF4-induced inhibition of cell migration/invasion. Consistently, KLF4 knockdown in HCC cells downregulated TIMP-1 and TIMP-2 expression, consequently promoting cell migration and invasion. Furthermore, we found that KLF4 regulated E-cadherin and epithelial-mesenchymal transition (EMT)-related proteins such as snail, vimentin and Bmi1 to modulate the cell migration ability. These results together demonstrated for the first time that KLF4 plays an important role in inhibiting the aggressiveness of HCC cells via upregulation of TIMP-1 and TIMP-2.

原文English
頁(從 - 到)439-446
頁數8
期刊Oncology Reports
34
發行號1
DOIs
出版狀態Published - 1 7月 2015

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