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KLF8 involves in TGF-beta-induced EMT and promotes invasion and migration in gastric cancer cells

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Abstract

Purpose

Krüppel-like factor 8 (KLF8), a downstream transcription factor of transforming growth factor-β1 (TGF-β1), has a role in tumorigenesis, tumor progress and epithelial-to-mesenchymal transition (EMT) induction. Recent studies mainly focused on its role in breast cancer and hepatocellular carcinoma; however, little is studied in gastric cancer. Here, we aim to explore whether KLF8 is involved in TGF-β1-induced EMT in gastric cancer cells.

Methods

Western blot and real-time PCR assays were used to detect the expression of KLF8, E-cadherin and vimentin in gastric cancer cell line SGC7901 treated with or without TGF-β1. The lentivirus-mediated RNA interference technique was used to knock down the expression of KLF8 in gastric cancer cell line SGC7901. In vitro, the ability of cell migration and invasion were measured by transwell and wound healing assays; the cell motility was detected by high content screening assay.

Results

TGF-β1 could induce EMT via down-regulating E-cadherin and up-regulating vimentin expression in gastric cancer cells. Further study found that TGF-β1 could induce KLF8 expression at the protein and mRNA levels in gastric cancer cells (P < 0.05). Western blot and real-time PCR assays found that small interference RNA (siRNA)-mediated KLF8 silence blocked TGF-β1-induced EMT-like transformation and subsequently reversed the loss of E-cadherin and gain of vimentin. In vitro, inhibition of KLF8 decreased TGF-β1-prompted cell migration, invasion and motility.

Conclusions

KLF8, a transcription factor, is involved in TGF-β1-induced EMT in gastric cancer cells and may be a novel therapeutic target for the treatment of gastric cancer.

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Abbreviations

KLF8:

Krüppel-like factor 8

TGF-β1:

Transforming growth factor-β

EMT:

Epithelial–mesenchymal transition

siRNA:

Small interference RNA

ECM:

Extra cellular matrix

cDNA:

Complementary DNA

mRNA:

Messenger RNA

GFP:

Green fluorescent protein

NC:

Negative control

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Acknowledgments

Grant sponsor: National Nature Science Foundation of China (Number: 81030044).

Conflict of interest

We have no conflict of interest to be disclosed.

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Authors and Affiliations

  1. State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, 15 West Changle Road, Xi’an, 710032, China

    Hui Zhang, Yafang Wang, Guohong Zhao, Changhao Liu, Xiao Xiao, Kaichun Wu, Yongzhan Nie, Hongbo Zhang & Daiming Fan

  2. Department of Oncology, Tangdu Hospital, Fourth Military Medical University, 1 Xinsi Road, Xi’an, 710038, China

    Lili Liu

  3. Institute of Neuroscience, The Fourth Military Medical University, 15 West Changle Road, Xi’an, 710032, China

    Rougang Xie

Authors
  1. Hui Zhang
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  2. Lili Liu
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  3. Yafang Wang
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  4. Guohong Zhao
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  5. Rougang Xie
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  6. Changhao Liu
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  7. Xiao Xiao
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  8. Kaichun Wu
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  9. Yongzhan Nie
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  10. Hongbo Zhang
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  11. Daiming Fan
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Corresponding authors

Correspondence to Hongbo Zhang or Daiming Fan.

Additional information

Hui Zhang and Lili Liu contributed equally to this work.

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Zhang, H., Liu, L., Wang, Y. et al. KLF8 involves in TGF-beta-induced EMT and promotes invasion and migration in gastric cancer cells. J Cancer Res Clin Oncol 139, 1033–1042 (2013). https://doi.org/10.1007/s00432-012-1363-3

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  • DOI: https://doi.org/10.1007/s00432-012-1363-3

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