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研究発表を行った学会；
　　　第90回日本薬理学会年会
　　　2017年3月15日〜17日（長崎市）
タイトル；Clinical and biological significance of tumor suppressor CYLD in oral squamous cell carcinoma.
発表者；金丸　歩美　氏
　　　（熊本大学　薬学教育部　臨床薬物動態学分野）
要旨；
Cylindromatosis (CYLD) is a tumor suppressor that regulates signaling pathways by acting as a deubiquitinating enzyme. Although recent study has shown that loss of functional CYLD is potentially-correlated with prognosis of patients with oral squamous cell carcinoma (OSCC), its clinical and biological significances are largely unknown. In this study, we sought to investigate and determine the role of CYLD in OSCC progression. In invasive region of OSCC tissues, CYLD expression was significantly reduced, whereas it was conserved in normal epithelium. In OSCC cells, CYLD knockdown by siRNA led to epithelial-mesenchymal transition (EMT) and increased migratory activity. Interestingly, CYLD knockdown significantly enhanced Smad3 phosphorylation in TGF-β signaling pathway through increasing TGF-βRI protein stability. Furthermore, LY2157299, a TGF-βRI kinase inhibitor, significantly suppress EMT-like changes caused by CYLD knockdown. Those results suggest that loss of functional CYLD may promote invasion through EMT-like changes via TGF-βRI stabilization in OSCC cells. Deeper understanding of more biological feature and clinical significance of CYLD may open up novel strategies for OSCC treatment.