索拉非尼
ALDH2
肝细胞癌
醛脱氢酶
蛋白质组
癌症研究
化学
背景(考古学)
药理学
生物化学
酶
医学
生物
古生物学
作者
Inês C. Ferreira,Estefania Torrejón,Bernardo Abecasis,Bruno M. Alexandre,Ricardo A. Gomes,Chris Verslype,Jos van Pelt,Ana Barbas,Daniel Simão,Tiago M. Bandeiras,Alessio Bortoluzzi,Sérgio Rebelo
标识
DOI:10.1016/j.slasd.2024.100154
摘要
Sorafenib is a multikinase inhibitor indicated for first-line treatment of unresectable hepatocellular carcinoma. Despite its widespread use in the clinic, the existing knowledge of sorafenib mode-of-action remains incomplete. To build upon the current understanding, we used the Cellular Thermal Shift Assay (CETSA) coupled to Mass Spectrometry (CETSA-MS) to monitor compound binding to its target proteins in the cellular context on a proteome-wide scale. Among the potential sorafenib targets, we identified aldehyde dehydrogenase 2 (ALDH2), an enzyme that plays a major role in alcohol metabolism. We validated the interaction of sorafenib with ALDH2 by orthogonal methods using pure recombinant protein, proving that this interaction is not mediated by other cellular components. Moreover, we showed that sorafenib inhibits ALDH2 activity, supporting a functional role for this interaction. Finally, we were able to demonstrate that both ALDH2 protein expression and activity were reduced in sorafenib-resistant cells compared to the parental cell line. Overall, our study allowed the identification of ALDH2 as a novel sorafenib target and sheds light on its potential role in both hepatocellular carcinoma and sorafenib resistance condition.
科研通智能强力驱动
Strongly Powered by AbleSci AI