Switching in discoid domain receptor expressions in SLUG-induced epithelial-mesenchymal transition

Authors

  • Michiko Maeyama MD,

    1. Research Center for Innovative Cancer Therapy and the 21st Century Center of Excellence Program for Medical Science, Kurume University, Kurume, Japan
    2. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
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  • Hironori Koga MD,

    Corresponding author
    1. Research Center for Innovative Cancer Therapy and the 21st Century Center of Excellence Program for Medical Science, Kurume University, Kurume, Japan
    2. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
    • Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan===

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    • Fax: (011) (81) 942 34 2623

  • Karuppaiyah Selvendiran PhD,

    1. Research Center for Innovative Cancer Therapy and the 21st Century Center of Excellence Program for Medical Science, Kurume University, Kurume, Japan
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  • Chikatoshi Yanagimoto MD,

    1. Research Center for Innovative Cancer Therapy and the 21st Century Center of Excellence Program for Medical Science, Kurume University, Kurume, Japan
    2. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
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  • Shinichiro Hanada MD,

    1. Research Center for Innovative Cancer Therapy and the 21st Century Center of Excellence Program for Medical Science, Kurume University, Kurume, Japan
    2. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
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  • Eitaro Taniguchi MD,

    1. Research Center for Innovative Cancer Therapy and the 21st Century Center of Excellence Program for Medical Science, Kurume University, Kurume, Japan
    2. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
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  • Takumi Kawaguchi MD,

    1. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
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  • Masaru Harada MD,

    1. Research Center for Innovative Cancer Therapy and the 21st Century Center of Excellence Program for Medical Science, Kurume University, Kurume, Japan
    2. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
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  • Takato Ueno MD,

    1. Research Center for Innovative Cancer Therapy and the 21st Century Center of Excellence Program for Medical Science, Kurume University, Kurume, Japan
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  • Michio Sata MD

    1. Research Center for Innovative Cancer Therapy and the 21st Century Center of Excellence Program for Medical Science, Kurume University, Kurume, Japan
    2. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
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Abstract

BACKGROUND.

Acquired features of cells under epithelial-mesenchymal transition (EMT) have not yet been fully identified. The current study was conducted to assess alterations in both the proliferative potential and the responsiveness to extracellular matrices (ECMs) in EMT.

METHODS.

MDCK cells and SLUG-transfected MDCK clones (SLUG-MDCK) were used in this study. The cell cycle was analyzed by using flow cytometry and Western blotting. ECM-stimulated cell proliferation was examined by using the following ECMs, type I collagen, type IV collagen, fibronectin, and laminin. Protein phosphorylation was detected by immunoprecipitation-Western by using the 4G10 antibody.

RESULTS.

Both G1 and G2/M arrest were found in the SLUG-MDCK cells, and the responsible molecules for the cell-cycle arrests were, at least in part, p21WAF1/Cip1 and Wee1. Once in contact with type I collagen, the SLUG-MDCK cells, showing the Wee1 degradation, dramatically started to proliferate up to 6-fold in cell number at Day 5, in contrast to only a 2-fold increase in the control. The analysis of the collagen receptors in the SLUG-MDCK cells disclosed a striking increase in the discoid domain receptor (DDR) 2 expression and a clear decrease in the DDR1 expression. The immunoprecipitated DDR2 protein extracted from SLUG-MDCK cells, which were cultured on collagen for 30 minutes, was tyrosine-phosphorylated, indicating valid functionality of the up-regulated receptor. The altered expression from DDR1 to DDR2 was also found in the naturally dedifferentiated sister cell lines of human liver cancer.

CONCLUSIONS.

Collectively, SLUG-induced EMT may alter the expression profile of receptor tyrosine kinases, including DDRs. Cancer 2008. © 2008 American Cancer Society.

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