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Regulation of Oral Squamous Cell Carcinoma Proliferation Through Crosstalk Between SMAD7 and CYLD

Wei-Li Ge, Jun-Feng Xu, Jun Hu

    Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
    |March 17, 2016
    PubMed
    Abstract

    Insights

    Cylindromatosis gene (CYLD) suppresses oral squamous cell carcinoma (OSCC) invasion by regulating SMAD7. Lower CYLD levels in OSCC correlate with poor survival, suggesting CYLD as a therapeutic target for preventing metastasis.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Cancer Research

    Background:

    • Transforming growth factor β (TGFβ) signaling regulates epithelial-mesenchymal transition and cancer cell invasiveness.
    • Dysfunctional protein ubiquitination is implicated in carcinogenesis.
    • The role of cylindromatosis gene (CYLD), a deubiquitinating enzyme, in oral squamous cell carcinoma (OSCC) invasion remains unclear.

    Purpose of the Study:

    • To investigate the role of CYLD in the regulation of OSCC cell invasion.
    • To determine the relationship between CYLD and SMAD7 in OSCC.

    Main Methods:

    • Analysis of CYLD and SMAD7 levels in clinical OSCC specimens and cell lines.
    • Manipulation of CYLD and SMAD7 expression in OSCC cells.
    • Assessment of cell invasiveness using transwell assays.
    • Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting to measure mRNA and protein levels.

    Main Results:

    • CYLD and SMAD7 levels were significantly decreased in OSCC tissues compared to normal tissues.
    • Lower CYLD and SMAD7 levels were observed in metastatic OSCC and correlated with poor patient survival.
    • CYLD regulates SMAD7 levels in OSCC cells, with CYLD overexpression inhibiting and CYLD depletion enhancing SMAD7-mediated invasion.

    Conclusions:

    • Suppression of CYLD in OSCC promotes SMAD7-mediated cancer invasion.
    • CYLD is a potential therapeutic target for preventing OSCC metastasis.

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