Bortezomib enhances radiosensitivity in oral cancer through inducing autophagy-mediated TRAF6 oncoprotein degradation

doi:10.1186/s13046-018-0760-0

CNU IR > Pharmacy and Science > Dept. of Cosmetic Science and institute of cosmetic science > Periodical Articles > 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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