RANBP9 and RANBP10 cooperate in regulating non-small cell lung cancer proliferation

作者：Arturo Orlacchio, Yasuko Kajimura, Lara Rizzotto, Anna Tessari, Shimaa Soliman, Rosa Visone, Liwen Zhang, Brian D. Fries, Lino Tessarollo, Joseph M. Amann, David P. Carbone, Alessia Lodi, Amer Ahmed, Ruggiero Gorgoglione, Giuseppe Fiermonte, Mike Freitas, Dario Palmieri, Jacob Kaufman, Vincenzo Coppola · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2025 · DOI：10.1186/s13046-025-03491-8 · 被引用次数：3 · 研究领域：Ubiquitin and proteasome pathways、Lung Cancer Treatments and Mutations、Cancer-related Molecular Pathways

BACKGROUND: RANBP9 and RANBP10, also called Scorpins, are essential components of the C-terminal to LisH (CTLH) complex, an evolutionarily conserved poorly investigated multisubunit E3 ligase. Their role in non-small cell lung cancer (NSCLC) is unknown. METHODS: In this study, first we used stable loss-of function and overexpression inducible cell lines to investigate the ability of either RANBP9 or RANBP10 to form their own functional CTLH complex. Then, we probed lysates from patient tumors and analyzed data from publicly available repositories to investigate the expression of RANBP9 and RANBP10. Finally, we used inducible cell lines in vitro to recapitulate the expression observed in patients and investigate the changes of the proteome and the ubiquitylome associated with either RANBP9 or RANBP10 in NSCLC. RESULTS: Here, we show that the two Scorpins are both expressed in NSCLC cells and that either of them can independently support the formation of the CTLH complex. Short-term experiments revealed that the RANBP9 and RANBP10 proteins balance each other in terms of expression, and the acute overexpression of one or the other results in significant reshaping of the NSCLC cell proteome and ubiquitylome. A higher RANBP9/RANBP10 ratio is associated with greater proliferation in both NSCLC cell lines and patients. Acute increased expression of RANBP10 slows NSCLC cell proliferation and decreases the level of proliferation-associated proteins, including key players in DNA replic...