Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/32164
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    Title: Bortezomib enhances radiosensitivity in oral cancer through inducing autophagy-mediated TRAF6 oncoprotein degradation
    Authors: Wu, Yuan-Hua
    Wu, Wun-Syuan
    Lin, Li-Ching
    Liu, Chiang-Shin
    Ho, Sheng-Yow
    Wang, Bour-Jr
    Huang, Bu-Miin
    Yeh, Ya-Ling
    Chiu, Hui-Wen
    Yang, Wei-Lei
    Wang, Ying-Jan
    Contributors: Natl Cheng Kung Univ, Dept Environm & Occupat Hlth, Coll Med
    Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Dept Radiat Oncol, Coll Med
    Chi Mei Med Ctr, Dept Radiat Oncol
    Taipei Med Univ, Sch Med
    Chung Hwa Univ Med Technol
    Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Dept Pathol, Coll Med
    Chi Mei Med Ctr, Dept Radiat Oncol
    Chang Jung Christian Univ
    Natl Cheng Kung Univ Hosp, Dept Occupat & Environm Med
    Chia Nan Univ Pharm & Sci, Dept Cosmet Sci
    Chia Nan Univ Pharm & Sci, Inst Cosmet Sci
    Natl Cheng Kung Univ, Coll Med, Dept Cell Biol & Anat
    Taipei Med Univ, Grad Inst Clin Med, Coll Med
    Taipei Med Univ, Shuang Ho Hosp, Dept Internal Med, Div Nephrol
    Univ Texas MD Anderson Canc Ctr
    Asia Univ, Dept Biomed Informat
    China Med Univ, China Med Univ Hosp, Dept Med Res
    Keywords: Oral squamous cell carcinoma
    Radiation
    TRAF6
    Ubiquitination
    Autophagy
    Date: 2018-04-27
    Issue Date: 2019-11-15 15:43:23 (UTC+8)
    Publisher: BIOMED CENTRAL LTD
    Abstract: Background: Oral squamous cell carcinoma (OSCC) is a malignant tumor that may occur anywhere within the oral cavity. The survival rate of OSCC patients has not improved over the past decades due to its heterogeneous etiology, genetic aberrations, and treatment outcomes. We investigated the role of tumor necrosis factor receptor-associated factor 6 (TRAF6) in OSCC cells treated with bortezomib (a proteasome inhibitor) combined with irradiation (IR) treatment. Methods: The effects of combined treatment in OSCC cells were investigated using assays of cell viability, autophagy, apoptosis, western blotting, and immunofluorescence staining. The ubiquitination of proteins was analyzed by immunoprecipitation. Stable knockdown of TRAF6 in OSCC cells was constructed with lentivirus. The xenograft murine models were used to observe tumor growth. Results: We found synergistic effects of bortezomib and IR on the viability of human oral cancer cells. The combination of bortezomib and IR treatment induced autophagic cell death. Furthermore, bortezomib inhibited IR-induced TRAF6 ubiquitination and inhibited TRAF6-mediated Akt activation. Bortezomib reduced TRAF6 protein expression through autophagy-mediated lysosomal degradation. TRAF6 played an oncogenic role in tumorigenesis of human oral cancer cells and oral tumor growth was suppressed by bortezomib and IR treatment. In addition, OSCC patients with expression of TRAF6 showed a trend towards poorer cancer-specific survival when compared with patients without TRAF6 expression. Conclusions: A combination of a proteasome inhibitor, IR treatment and TRAF6 inhibition could be a novel therapeutic strategy in OSCC.
    ???metadata.dc.relation.uri???: http://dx.doi.org/10.1186/s13046-018-0760-0
    Relation: Journal of Orthopaedic Surgery and Research, v.37, 91
    Appears in Collections:[Dept. of Cosmetic Science and institute of cosmetic science] Periodical Articles

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