肝细胞癌
转移
癌症研究
生物
医学
内科学
癌症
作者
Qianqian Liu,Wang Jun-hua,Huizi Sun,Zhenhua Zhang,Hong Wang,Shuai Ma,Chenxi Zhang,Qianqian Wang,Guodi Cai,Jie Zheng,Yichu Nie,Peiqing Liu,Junjian Wang
标识
DOI:10.1016/j.ymthe.2024.01.032
摘要
Abstract
Approximately 80%-90% of hepatocellular carcinomas (HCC) occur in a premalignant environment of fibrosis and abnormal extracellular matrix (ECM), highlighting an essential role of ECM in the tumorigenesis and progress of HCC. However, the determinants of ECM in HCC are poorly defined. Here, we show that nuclear receptor RORγ is highly expressed and amplified in HCC tumors. RORγ functions as an essential activator of the matrisome program via directly driving the expression of major ECM genes in HCC cells. The elevated RORγ increases fibronectin-1 deposition, cell-matrix adhesion and collagen production, creating a favorable microenvironment to boost liver cancer metastasis. Moreover, RORγ antagonists effectively inhibit tumor growth and metastasis in multiple HCC xenografts and immune-intact models, and they effectively sensitize HCC tumors to sorafenib therapy in mice. Notably, the elevated RORγ expression is associated with ECM remodeling and metastasis in patients with HCC. Taken together, we identify RORγ as a key player of ECM remodeling in HCC and as an attractive therapeutic target for advanced HCC.
科研通智能强力驱动
Strongly Powered by AbleSci AI