EMMPRIN regulates cytoskeleton reorganization and cell adhesion in prostate cancer

Authors

  • Haining Zhu,

    1. Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky
    2. Department of Toxicology, College of Medicine, University of Kentucky, Lexington, Kentucky
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  • Jun Zhao,

    1. Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky
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  • Beibei Zhu,

    1. Division of Urology, Department of Surgery, College of Medicine, University of Kentucky, Lexington, Kentucky
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  • Joanne Collazo,

    1. Department of Toxicology, College of Medicine, University of Kentucky, Lexington, Kentucky
    2. Division of Urology, Department of Surgery, College of Medicine, University of Kentucky, Lexington, Kentucky
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  • Jozsef Gal,

    1. Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky
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  • Ping Shi,

    1. Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky
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  • Li Liu,

    1. Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky
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  • Anna-Lena Ström,

    1. Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky
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  • Xiaoning Lu,

    1. Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky
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  • Richard O. McCann,

    1. Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky
    Current affiliation:
    1. Division of Basic Medical Sciences, Mercer University School of Medicine, 1550 College Street, Macon, GA 31207.
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  • Michal Toborek,

    1. Department of Neurosurgery, College of Medicine, University of Kentucky, Lexington, Kentucky
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  • Natasha Kyprianou

    Corresponding author
    1. Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky
    2. Department of Toxicology, College of Medicine, University of Kentucky, Lexington, Kentucky
    3. Division of Urology, Department of Surgery, College of Medicine, University of Kentucky, Lexington, Kentucky
    • Division of Urology, Combs Res. Bldg. Rm. 306, University of Kentucky Medical Center, Lexington, KY 40536.
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Abstract

BACKGROUND

Proteins on cell surface play important roles during cancer progression and metastasis via their ability to mediate cell-to-cell interactions and navigate the communication between cells and the microenvironment.

METHODS

In this study a targeted proteomic analysis was conducted to identify the differential expression of cell surface proteins in human benign (BPH-1) versus malignant (LNCaP and PC-3) prostate epithelial cells. We identified EMMPRIN (extracellular matrix metalloproteinase inducer) as a key candidate and shRNA functional approaches were subsequently applied to determine the role of EMMPRIN in prostate cancer cell adhesion, migration, invasion as well as cytoskeleton organization.

RESULTS

EMMPRIN was found to be highly expressed on the surface of prostate cancer cells compared to BPH-1 cells, consistent with a correlation between elevated EMMPRIN and metastasis found in other tumors. No significant changes in cell proliferation, cell cycle progression, or apoptosis were detected in EMMPRIN knockdown cells compared to the scramble controls. Furthermore, EMMPRIN silencing markedly decreased the ability of PC-3 cells to form filopodia, a critical feature of invasive behavior, while it increased expression of cell–cell adhesion and gap junction proteins.

CONCLUSIONS

Our results suggest that EMMPRIN regulates cell adhesion, invasion, and cytoskeleton reorganization in prostate cancer cells. This study identifies a new function for EMMPRIN as a contributor to prostate cancer cell–cell communication and cytoskeleton changes towards metastatic spread, and suggests its potential value as a marker of prostate cancer progression to metastasis. Prostate 72:72–81, 2012. © 2011 Wiley Periodicals, Inc.

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