Arginyl-tRNA-protein transferase 1 (ATE1) promotes melanoma cell growth and migration

FEBS Letters

article

Ikrame Lazar¹  Bertrand Fabre²  Yongmei Feng¹  Ali Khateb¹  Philippe Frit⁵  Anna Kashina⁶  Tongwu Zhang⁷  Emily Avitan-Hersh²  Hyungsoo Kim¹  Kevin Brown⁷  Ivan Topisirovic⁸  Ze’ev A. Ronai¹ 

[1] Sanford Burnham Prebys Medical Discovery Institute;Technion Integrated Cancer Center, Faculty of Medicine, Technion Institute of Technology;MCD, Centre de Biologie Intégrative ,(CBI), CNRS, UT3, Université de Toulouse;Laboratoire de Recherche en Sciences Végétales, UMR5546, UT3, INP, CNRS, Université de Toulouse;Institut de Pharmacologie et de Biologie Structurale ,(IPBS), UMR 5089, CNRS, UT3, Université de Toulouse;Department of Biomedical Sciences, University of Pennsylvania;Division of Cancer Epidemiology and Genetics, National Cancer Institute;Gerald Bronfman Department of Oncology, Departments of Experimental Medicine and Biochemistry, Lady Davis Institute, Sir Mortimer B. Davis Jewish General Hospital, McGill University

关键词: ATE1;    AXIN1;    cancer;    cell migration;    cell viability;    melanoma;   

DOI  :  10.1002/1873-3468.14376

来源: John Wiley & Sons Ltd.

【 摘 要 】

Arginyl-tRNA-protein transferase 1 (ATE1) catalyses N-terminal protein arginylation, a post-translational modification implicated in cell migration, invasion and the cellular stress response. Herein, we report that ATE1 is overexpressed in NRAS-mutant melanomas, while it is downregulated in BRAF-mutant melanomas. ATE1 expression was higher in metastatic tumours, compared with primary tumours. Consistent with these findings, ATE1 depletion reduced melanoma cell viability, migration and colony formation. Reduced ATE1 expression also affected cell responses to mTOR and MEK inhibitors and to serum deprivation. Among putative ATE1 substrates is the tumour suppressor AXIN1, pointing to the possibility that ATE1 may fine-tune AXIN1 function in melanoma. Our findings highlight an unexpected role for ATE1 in melanoma cell aggressiveness and suggest that ATE1 constitutes a potential new therapeutic target.

【 授权许可】

Unknown