USP4-mediated CENPF deubiquitylation regulated tumor metastasis in colorectal cancer

doi:10.1038/s41419-025-07424-3

科研成果详情

题名	USP4-mediated CENPF deubiquitylation regulated tumor metastasis in colorectal cancer
作者	Zhongdong Xie1,2; Hanbin Lin 3,4; Yuecheng Wu 4; Yanan Yu 5; Xintong Liu6; Yating Zheng2; Xiaojie Wang 1; Jiashu Wu 7; Meifang Xu 8; Yuting Han 4; Qiongying Zhang 9; Yu Deng 1; Lin Lin 8; Yan Linzhu 1; Li Qingyun 1; Xinjian Lin 10; Ying Huang 11; Pan Chi 12
发表日期	2025-02-08
发表期刊	Cell death & disease 影响因子和分区
语种	英语
原始文献类型	Journal Article
摘要	Metastasis is a major challenge for colorectal cancer (CRC) treatment. In this study, we identified autophagy activation as a prognostic indicator in CRC and observed that the expression of key autophagy proteins is elevated in metastatic and recurrent cases. Our subsequent goal was to identify potential genes associated with the autophagy panel and assess their prognostic significance, biological roles, and mechanisms in CRC metastasis. Among the candidates, CENPF emerged as the top gene in our screening process. We found that CENPF expression was preferentially elevated in CRC tissues compared to adjacent normal tissues, with significantly higher levels in CRC patients with tumor recurrence. Furthermore, a multicenter cohort study demonstrated that upregulated CENPF expression was strongly associated with poorer disease-free survival in CRC. Functional experiments showed that CENPF knockdown inhibited CRC cell invasion and metastasis both in vitro and in vivo. Intriguingly, we found CENPF undergoes degradation in CRC via the ubiquitination-proteasome pathway. Mechanistically, we observed that USP4 interacted with and stabilized CENPF via deubiquitination. Furthermore, USP4-mediated CENPF upregulation was critical regulators of metastasis of CRC. Examination of clinical samples confirmed that USP4 expression positively correlates with CENPF protein expression, but not mRNA transcript levels. Taken together, this study describes a novel USP4-CENPF signaling axis which is crucial for CRC metastasis, potentially serving as a therapeutic target and a promising prognostic biomarker for CRC.
卷号	16 期号:1
DOI	10.1038/s41419-025-07424-3
收录类别	PUBMED
URL	查看原文
PubMed ID	39922805
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/225850
专题	附属第一医院附属第一医院_病理科第一临床医学院（信息与工程学院）、附属第一医院_中心实验室
作者单位	1.Department of Colorectal Surgery, Union Hospital, Fujian Medical University, Fuzhou, China.; 2.Department of Colorectal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.; 3.Central Laboratory, Affiliated Hospital of Putian University, Putian, China.; 4.Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China.; 5.Guilin Medical University, Guilin, China.; 6.Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.; 7.Department of Science and Technology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.; 8.Department of Pathology, Union Hospital, Fujian Medical University, Fuzhou, China.; 9.Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.; 10.Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China. xlin@fjmu.edu.cn.; 11.Department of Colorectal Surgery, Union Hospital, Fujian Medical University, Fuzhou, China. fjxhhy@sina.com.; 12.Department of Colorectal Surgery, Union Hospital, Fujian Medical University, Fuzhou, China. chipanfjxh@163.com.
第一作者单位	附属第一医院
推荐引用方式 GB/T 7714	Zhongdong Xie,Hanbin Lin,Yuecheng Wu,et al. USP4-mediated CENPF deubiquitylation regulated tumor metastasis in colorectal cancer[J]. Cell death & disease,2025,16(1).
APA	Zhongdong Xie., Hanbin Lin., Yuecheng Wu., Yanan Yu., Xintong Liu., ... & Pan Chi. (2025). USP4-mediated CENPF deubiquitylation regulated tumor metastasis in colorectal cancer. Cell death & disease, 16(1).
MLA	Zhongdong Xie,et al."USP4-mediated CENPF deubiquitylation regulated tumor metastasis in colorectal cancer".Cell death & disease 16.1(2025).