伦瓦提尼
癌症研究
上皮-间质转换
化学
信号转导
医学
内科学
肿瘤科
癌症
肝细胞癌
转移
索拉非尼
生物化学
作者
Liming Deng,Wenming Bao,Baofu Zhang,Sina Zhang,Ziyan Chen,Xuewen Zhu,Bangjie He,Lijun Wu,Xiaohu Chen,Tuo Deng,Bo Chen,Zhengping Yu,Yi Wang,Gang Chen
标识
DOI:10.1038/s41419-023-06092-5
摘要
Intrahepatic cholangiocarcinoma (ICC) is a primary liver malignancy and is characterized by highly aggressive and malignant biological behavior. Currently, effective treatment strategies are limited. The effect of lenvatinib on ICC is unknown. In this study, we found that AZGP1 was the key target of lenvatinib in ICC, and its low expression in ICC cancer tissues was associated with a poor prognosis in patients. Lenvatinib is a novel AZGP1 agonist candidate for ICC that inhibits ICC-EMT by regulating the TGF-β1/Smad3 signaling pathway in an AZGP1-dependent manner. Furthermore, we found that lenvatinib could increase AZGP1 expression by increasing the acetylation level of H3K27Ac in the promoter region of the AZGP1 gene, thereby inhibiting EMT in ICC cells. In conclusion, lenvatinib activates AZGP1 by increasing the acetylation level of H3K27Ac on the AZGP1 promoter region and regulates the TGF-β1/Smad3 signaling pathway in an AZGP1-dependent manner to inhibit ICC-EMT. This study offers new insight into the mechanism of lenvatinib in the treatment of ICC and provides a theoretical basis for new treatment methods.
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