title: SENP2 regulated the stability of β-catenin through WWOX in hepatocellular carcinoma cell.
abstract: SUMOylation and deSUMOylation are dynamic mechanisms regulating a spectrum of protein activities. The SUMO proteases (SENP) remove SUMO conjugate from proteins, and their expression is deregulated in cancers. SENP2 has been reported to play a critical role in the control of hepatocellular carcinoma (HCC) cell growth by modulating the stability of β-catenin. However, the underlying mechanism remains largely unknown. Here, we show that the WW domain-containing oxidoreductase (WWOX), a novel inhibitor of the Wnt/β-catenin pathway, is required for stabilization of β-catenin regulated by SENP2 in HCC cells. The transcriptional level of WWOX is tightly regulated by SENP2. Moreover, knockdown of WWOX by siRNA attuned SENP2-induced β-catenin degradation and decreased SENP2-mediated HCC cell proliferation arrest. Taken together, our data suggested that WWOX is a key downstream modulator of the SENP2 tumor suppressor function in HCC cell.
authors: Department of Hepatobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou, 450003, Henan, China.
authors: Qing-Feng
authors: QF
authors: Jiang
authors: Yu-Wei
authors: YW
authors: Tian
authors: Quan
authors: Q
authors: Shen
authors: Huan-Zhou
authors: HZ
authors: Xue
authors: Ke
authors: K
authors: Li
mesh_terms: D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D000074584:WW Domain-Containing Oxidoreductase; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human; D003546:Cysteine Endopeptidases; C501833:SENP2 protein, human