Chrysin serves as a novel inhibitor of DGKα/FAK interaction to suppress the malignancy of esophageal squamous cell carcinoma(ESCC)
Chrysin serves as a novel inhibitor of DGKα/FAK interaction to suppress the malignancy of esophageal squamous cell carcinoma(ESCC)作者机构:Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing)Laboratory of Molecular OncologyPeking University Cancer Hospital&InstituteBeijing 100142China
出 版 物:《Acta Pharmaceutica Sinica B》 (药学学报(英文版))
年 卷 期:2021年第11卷第1期
页 面:143-155页
核心收录:
学科分类:1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
基 金:supported by the National Natural Science Foundation of China(81830086,81988101,81772504 and 81972243) Beijing Municipal Commission of Health and Family Planning Project(PXM2018_026279_000005,China)
主 题:Chrysin Esophageal squamous cell carcinoma DGKα FAK Proteineprotein interactions
摘 要:Among current novel druggable targets,proteineprotein interactions(PPIs)are of considerable and growing *** kinase a(DGKα)interacts with focal adhesion kinase(FAK)band 4.1-ezrin-radixin-moesin(FERM)domain to induce the phosphorylation of FAK Tyr397 site and promotes the malignant progression of esophageal squamous cell carcinoma(ESCC)*** is a multi-functional bioactive flavonoid,and possesses potential anticancer activity,whereas little is known about the anticancer activity and exact molecular mechanisms of chrysin in ESCC *** this study,we found that chrysin significantly disrupted the DGKα/FAK signalosome to inhibit FAKcontrolled signaling pathways and the malignant progression of ESCC cells both in vitro and in vivo,whereas produced no toxicity to the normal *** validation specifically demonstrated that Asp435 site in the catalytic domain of DGKαcontributed to chrysin-mediated inhibition of the assembly of DGKα/FAK *** study has illustrated DGKα/FAK complex as a target of chrysin for the first time,and provided a direction for the development of natural products-derived PPIs inhibitors in tumor treatment.