Loss of UFL1 drives chromosome instability and tumorigenesis of prostate cancer
Abstract
Chromosomal instability (CIN) is a prevalent form of genomic instability in prostate cancer (PCa). However, its molecular mechanisms remain inadequately understood. This study demonstrates that reduced expression of UFM1-ligase 1 (UFL1) is commonly observed in PCa and correlates with elevated CIN rates. UFL1 deficiency results in severe mitotic defects, errors in chromosome segregation, and aneuploidy, thereby promoting malignant transformation. Mechanistically, UFL1 interacts with RNF20 and catalyzes its UFMylation, which enhances RNF20 binding to CEP192, facilitating its centrosomal localization and supporting mitotic spindle assembly. Additionally, downregulation of the microphthalmia-associated transcription factor (MITF) exacerbates PCa aggressiveness by suppressing UFL1 expression. These findings identify the MITF–UFL1–RNF20 axis as a critical regulator of spindle integrity and a potential therapeutic target in PCa.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (10)
Jimin Li
Department of Clinical Laboratory, Centre for Leading Medicine and Advanced Technologies of Institute of Health and Medicine, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China
Fang Yang
State Key Laboratory of Inorganic Synthesis and Preparative Chemistry College of Chemistry
Xiao Zhang
Liangfei Xu
Department of Clinical Laboratory, Centre for Leading Medicine and Advanced Technologies of Institute of Health and Medicine, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China
Hui Zheng
Department of Clinical Laboratory, Centre for Leading Medicine and Advanced Technologies of Institute of Health and Medicine, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China
Liu Liu
Shanghai Yuhui Pharmaceutical Technology (Group) Co., Ltd.
Xin Wan
School of Materials Science and Engineering
Tao Xu
Guanmin Jiang
Department of Clinical Laboratory, The Fifth Affiliated Hospital, Sun Yat-sen University
Hao Wang
Division of Quantitative Sciences, Department of Oncology Johns Hopkins University School of Medicine Baltimore Maryland USA