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Gastrokine 1 functions as a tumor suppressor by inhibition of epithelial–mesenchymal transition in gastric cancers

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Abstract

Purpose

Gastrokine 1 (GKN1) plays an important role in the gastric mucosal defense mechanism and also acts as a functional gastric tumor suppressor. The specific aim of this study was to determine the molecular mechanisms underlying GKN1 tumor suppressor activity in the progression of gastric cancers.

Methods

We examined the effect of GKN1 on epithelial–mesenchymal transition (EMT) and cell migration in GKN1-transfected and recombinant GKN1-treated AGS gastric cancer cells using in vitro wound healing, microchemotaxis, and invasion assays.

Results

In GKN1-transfected AGS cells, we observed inhibition of cell migration and invasion in wound healing, transwell and Matrigel assay. Also, GKN1-transfected and recombinant GKN1-treated AGS cells showed decreased levels of ROS and expression of phosphatidylinositol 3-kinase (PI3K)/Akt pathway proteins, concomitant with re-expression of E-cadherin and decreased expression of cytoplasmic and nuclear expression of β-catenin, slug, snail, fibronectin, and vimentin.

Conclusions

These data suggest that the GKN1 gene may play an important role in the progression of sporadic gastric cancers via inhibition of EMT and cancer cell migration.

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Abbreviations

GKN:

Gastrokine

EMT:

Epithelial–mesenchymal transition

ROS:

Reactive oxygen species

PBS:

Phosphor-buffered saline

PVDF:

Polyvinylidene difluoride

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Acknowledgments

We thank Dr. In Beom Kim at Department of Anatomy, College of Medicine, The Catholic University of Korea, for helpful discussion. This work was supported by the Happy tech. program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0020764).

Conflict of interest

The authors have no conflicts to disclose.

Author information

Authors and Affiliations

  1. Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul, 137-701, South Korea

    Jung Hwan Yoon, Young Hwi Kang, Yoo Jin Choi, Suk Woo Nam, Jung Young Lee & Won Sang Park

  2. Department of General Surgery, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul, 137-701, South Korea

    In Soo Park

  3. College of Pharmacy, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul, 120-750, South Korea

    Yun Sil Lee

  4. Division of Life Science and Pharmaceuticals, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul, 120-750, South Korea

    Yun Sil Lee

Authors
  1. Jung Hwan Yoon
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  2. Young Hwi Kang
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  3. Yoo Jin Choi
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  4. In Soo Park
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  5. Suk Woo Nam
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Corresponding author

Correspondence to Won Sang Park.

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432_2011_1051_MOESM1_ESM.tif

Effect of GKN1 recombinant protein on cell migration in AGS cancer cells. A scratch wound healing assay demonstrated that cell migration into the wound area was significantly inhibited in cells treated with recombinant GKN1 compared to control in a dose-dependent manner. The dotted lines indicate the original edges of the scratch defect. (TIFF 765 kb)

432_2011_1051_MOESM2_ESM.tif

The effect of GKN1 recombinant protein on cellular ROS levels. Treatment of GKN1 recombinant protein significantly decreased ROS levels in AGS cells in a dose-dependent manner. The results are presented as mean ± SD of a triplicate from a representative experiment. (TIFF 337 kb)

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Yoon, J.H., Kang, Y.H., Choi, Y.J. et al. Gastrokine 1 functions as a tumor suppressor by inhibition of epithelial–mesenchymal transition in gastric cancers. J Cancer Res Clin Oncol 137, 1697–1704 (2011). https://doi.org/10.1007/s00432-011-1051-8

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  • DOI: https://doi.org/10.1007/s00432-011-1051-8

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