泛素连接酶
泛素
下调和上调
癌症研究
结直肠癌
上皮-间质转换
信号转导
生物
癌症
转移
细胞生物学
遗传学
基因
作者
Jiani Yang,Yuanyu Liao,Bojun Wang,Luying Cui,Xuefan Yu,Feng Wu,Yanqiao Zhang,Ruiqi Liu,Yuanfei Yao
出处
期刊:Cancer Letters
[Elsevier]
日期:2023-11-01
卷期号:577: 216427-216427
被引量:4
标识
DOI:10.1016/j.canlet.2023.216427
摘要
Tumor cell migration, specifically epithelial-mesenchymal transition (EMT), serves as a key contributor to treatment failure in colon cancer patients. However, the limited comprehension of its genetic and biological aspects presents challenges for its investigation. EDAR-associated death domain (EDARADD), an important TNFR superfamily member, is elevated in colon cancer. However, it remains unclear about the exact role of EDARADD in the progression of colon cancer metastasis. In this study, we initially demonstrated that both protein and mRNA levels of EDDARADD are elevated in colon cancer tissues and cells, associated with reduced overall survival. Furthermore, functional experiments demonstrated that EDARADD promotes colon cancer cell proliferation and participates in EMT both in vitro and vivo. Mechanistically, Co-IP verified EDARADD could stabilize Snail1 by interacting with E3 ubiquitin ligase Trim21 to inhibit ubiquitination of Snail1. Interestingly, RNA-seq and ubiquitination assay revealed EDARADD's dual downregulation of Trim21 expression at the translational level via Cul1-mediated ubiquitin degradation, and at the transcriptional level through PPARa regulation. Moreover, EDARADD activates NF-κB signaling and experiences feedback transcriptional regulation by p65. In conclusion, this study highlights the signal pathway of EDARADD-PPARa-Trim21-Snail1-EMT and a feedback regulation of NF-κB signaling on EDARADD, which indicated EDARADD as an emerging therapeutic target for colon cancer.
科研通智能强力驱动
Strongly Powered by AbleSci AI