Krüppel-like factor 4 negatively regulates β-catenin expression and inhibits the proliferation, invasion and metastasis of gastric cancer

  • Authors:
    • Neng Zhang
    • Jun Zhang
    • Leiyuan Shuai
    • Lang Zha
    • Miao He
    • Zhen Huang
    • Ziwei Wang
  • View Affiliations

  • Published online on: March 7, 2012     https://doi.org/10.3892/ijo.2012.1395
  • Pages: 2038-2048
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Abstract

Krüppel-like factor 4 (KLF4) is a zinc-finger protein that plays an important role in the progression of gastric carcinoma. The abnormal activation of β-catenin frequently occurs in gastric cancer and has been associated with the promotion of tumor growth, invasion and metastasis. However, the potential interaction between KLF4 and β-catenin during gastric cancer development is unknown. In this study, a lentiviral KLF4 expression vector was constructed and utilized to transfect the human gastric cancer cell lines, SGC-7901, BGC-823, MKN-28 and MKN-45. KLF4 and β-catenin expression levels were measured by quantitative real-time RT-PCR and western blot analysis. Cell proliferation, colony formation and invasive potential were determined in the KLF4-transfected gastric cancer cells. The expression of E-cadherin and matrix metallopeptidase 2 (MMP2) was determined by western blot analysis. The overexpression of KLF4 significantly inhibited the expression of β-catenin in the MKN-45 gastric cancer cells. The restored expression of KLF4 suppressed proliferation, colony formation and inhibited the invasion and metastatic properties of MKN-45 gastric cancer cells. Furthermore, the forced expression of KLF4 in gastric tumor cell lines restored E-cadherin expression and inhibited MMP2 expression. Consistent with the in vitro findings, the enforced expression of the KLF4 gene in MKN-45 gastric carcinoma cells by lentiviral vector-mediated gene transfer effectively suppressed tumor growth in vivo. Our results show that KLF4 inhibits β-catenin expression and regulates the β-catenin-mediated biological behaviors of gastric cancer cells. The modulation of KLF4 expression may represent a novel therapeutic approach for β-catenin-driven malignancies.

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June 2012
Volume 40 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Zhang N, Zhang J, Shuai L, Zha L, He M, Huang Z and Wang Z: Krüppel-like factor 4 negatively regulates β-catenin expression and inhibits the proliferation, invasion and metastasis of gastric cancer. Int J Oncol 40: 2038-2048, 2012
APA
Zhang, N., Zhang, J., Shuai, L., Zha, L., He, M., Huang, Z., & Wang, Z. (2012). Krüppel-like factor 4 negatively regulates β-catenin expression and inhibits the proliferation, invasion and metastasis of gastric cancer. International Journal of Oncology, 40, 2038-2048. https://doi.org/10.3892/ijo.2012.1395
MLA
Zhang, N., Zhang, J., Shuai, L., Zha, L., He, M., Huang, Z., Wang, Z."Krüppel-like factor 4 negatively regulates β-catenin expression and inhibits the proliferation, invasion and metastasis of gastric cancer". International Journal of Oncology 40.6 (2012): 2038-2048.
Chicago
Zhang, N., Zhang, J., Shuai, L., Zha, L., He, M., Huang, Z., Wang, Z."Krüppel-like factor 4 negatively regulates β-catenin expression and inhibits the proliferation, invasion and metastasis of gastric cancer". International Journal of Oncology 40, no. 6 (2012): 2038-2048. https://doi.org/10.3892/ijo.2012.1395