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

• DOI: 10.1038/s41392-020-0181-3
• Publication Date: 2020-06-16T23:06:10Z
• Authors: 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
• Keywords: Abcg2; KLF4

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