The deubiquitylase UCHL3 maintains cancer stem-like properties by stabilizing the aryl hydrocarbon receptor

作     者：Lianlian Ouyang Bin Yan Yating Liu Chao Mao Min Wang Na Liu Zuli Wang Shouping Liu Ying Shi Ling Chen Xiang Wang Yan Cheng Ya Cao Desheng Xiao Lingqiang Zhang Shuang Liu Yongguang Tao Lianlian Ouyang;Bin Yan;Yating Liu;Chao Mao;Min Wang;Na Liu;Zuli Wang;Shouping Liu;Ying Shi;Ling Chen;Xiang Wang;Yan Cheng;Ya Cao;Desheng Xiao;Lingqiang Zhang;Shuang Liu;Yongguang Tao

作者机构：Department of OncologyInstitute of Medical SciencesNational Clinical Research Center for Geriatric DisordersXiangya HospitalCentral South University410008 ChangshaHunanChina Key Laboratory of Carcinogenesis and Cancer InvasionMinistry of EducationDepartment of PathologyXiangya HospitalCentral South University410078 ChangshaHunanChina Key Laboratory of Carcinogenesis of the Ministry of HealthCancer Research InstituteSchool of Basic MedicineCentral South University410078 ChangshaHunanChina Department of Thoracic SurgeryHunan Key Laboratory of Tumor Models and Individualized MedicineSecond Xiangya HospitalCentral South UniversityChangshaChina Xiangya School of Pharmaceutical SciencesCentral South University410008 ChangshaChina Department of PathologyXiangya HospitalCentral South University410008 ChangshaHunanChina State Key Laboratory of ProteomicsNational Center for Protein Sciences(Beijing)Beijing Institute of Lifeomics100850 BeijingChina 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2020年第5卷第1期

页      面：1609-1622页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：The National Natural Science Foundation of China(81672991 and 81874139[S.L.],81672787[Y.T.],81672308[X.W.]) the National Basic Research Program of China(2015CB553903[Y.T.])supported this study 

主　　题：lung markedly chemotherapy 

摘      要：Cancer stem cells(CSCs)exhibit highly aggressive and metastatic features and resistance to chemotherapy and *** hydrocarbon receptor(AhR)expression varies among non-small cell lung cancers(NSCLCs),and the mechanisms that support abnormal AhR expression in CSCs remain ***,we identified ubiquitin carboxyl terminal hydrolase L3(UCHL3),a DUB enzyme in the UCH protease family,as a bona fide deubiquitylase of the AhR in ***3 was shown to interact with,deubiquitylate,and stabilize AhR in a manner dependent on its deubiquitylation ***,we showed that UCHL3 promotes the stem-like characteristics and potent tumorigenic capacity of NSCLC ***3 increased AhR stability and the binding of AhR to the promoter regions of the“stemnessgenes ATP-binding cassette subfamily G member 2(ABCG2),KLF4,and *** of UCHL3 markedly downregulated the“stemnessgenes ABCG2,KLF4,and c-Myc,leading to the loss of selfrenewal and tumorigenesis in ***,the UCHL3 inhibitor TCID induced AhR degradation and exhibited significantly attenuated efficacy in NSCLC cells with stem cell-like ***,UCHL3 was shown to indicate poor prognosis in patients with lung *** general,our results reveal that the UCHL3 deubiquitylase is pivotal for AhR protein stability and a potential target for NSCLC-targeted therapy.