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Article

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

  • Authors:
    • Ming-Ta Sung
    • Hui-Tzu Hsu
    • Chih-Chun Lee
    • Hsin-Chen Lee
    • Ying‑Ju Kuo
    • Kate Hua
    • Cheng-Yuan Hsia
    • Chin-Wen Chi
  • View Affiliations / Copyright

    Affiliations: Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C., Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C., Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C., Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
  • Pages: 439-446
    |
    Published online on: May 8, 2015
       https://doi.org/10.3892/or.2015.3964
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Abstract

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.
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Copy and paste a formatted citation
Spandidos Publications style
Sung M, Hsu H, Lee C, Lee H, Kuo YJ, Hua K, Hsia C and Chi C: Krüppel-like factor 4 modulates the migration and invasion of hepatoma cells by suppressing TIMP-1 and TIMP-2. Oncol Rep 34: 439-446, 2015.
APA
Sung, M., Hsu, H., Lee, C., Lee, H., Kuo, Y., Hua, K. ... Chi, C. (2015). Krüppel-like factor 4 modulates the migration and invasion of hepatoma cells by suppressing TIMP-1 and TIMP-2. Oncology Reports, 34, 439-446. https://doi.org/10.3892/or.2015.3964
MLA
Sung, M., Hsu, H., Lee, C., Lee, H., Kuo, Y., Hua, K., Hsia, C., Chi, C."Krüppel-like factor 4 modulates the migration and invasion of hepatoma cells by suppressing TIMP-1 and TIMP-2". Oncology Reports 34.1 (2015): 439-446.
Chicago
Sung, M., Hsu, H., Lee, C., Lee, H., Kuo, Y., Hua, K., Hsia, C., Chi, C."Krüppel-like factor 4 modulates the migration and invasion of hepatoma cells by suppressing TIMP-1 and TIMP-2". Oncology Reports 34, no. 1 (2015): 439-446. https://doi.org/10.3892/or.2015.3964
Copy and paste a formatted citation
x
Spandidos Publications style
Sung M, Hsu H, Lee C, Lee H, Kuo YJ, Hua K, Hsia C and Chi C: Krüppel-like factor 4 modulates the migration and invasion of hepatoma cells by suppressing TIMP-1 and TIMP-2. Oncol Rep 34: 439-446, 2015.
APA
Sung, M., Hsu, H., Lee, C., Lee, H., Kuo, Y., Hua, K. ... Chi, C. (2015). Krüppel-like factor 4 modulates the migration and invasion of hepatoma cells by suppressing TIMP-1 and TIMP-2. Oncology Reports, 34, 439-446. https://doi.org/10.3892/or.2015.3964
MLA
Sung, M., Hsu, H., Lee, C., Lee, H., Kuo, Y., Hua, K., Hsia, C., Chi, C."Krüppel-like factor 4 modulates the migration and invasion of hepatoma cells by suppressing TIMP-1 and TIMP-2". Oncology Reports 34.1 (2015): 439-446.
Chicago
Sung, M., Hsu, H., Lee, C., Lee, H., Kuo, Y., Hua, K., Hsia, C., Chi, C."Krüppel-like factor 4 modulates the migration and invasion of hepatoma cells by suppressing TIMP-1 and TIMP-2". Oncology Reports 34, no. 1 (2015): 439-446. https://doi.org/10.3892/or.2015.3964
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