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

Jung Hwan Yoon, Young Hwi Kang, Yoo Jin Choi, In Soo Park, Suk Woo Nam, Jung Young Lee, Yun Sil Lee, Won Sang Park

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

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.

Original languageEnglish
Pages (from-to)1697-1704
Number of pages8
JournalJournal of Cancer Research and Clinical Oncology
Volume137
Issue number11
DOIs
StatePublished - Nov 2011

Bibliographical note

Funding Information:
significantly reduced intracellular ROS levels by increased expression of antioxidative stress genes, MnSOD and catalase, and decreased expression of PI3K. The results are presented as mean ± SD of a triplicate experiment. d GKN1 induced increased expression of GSK3α/β, but decreased expression of p-Akt. Conversely, knock-down of GKN1 expression with siRNA suppressed GSK3α/β and increased p-Akt expression 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).

Keywords

  • EMT
  • GKN1
  • Gastric cancer
  • Progression
  • Tumor suppressor

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