Chrysin serves as a novel inhibitor of DGKα/FAK interaction to suppress the malignancy of esophageal squamous cell carcinoma(ESCC)

作     者：Jie Cheny Yan Wangy Di Zhao Lingyuan Zhang Weimin Zhang Jiawen Fan Jinting Li Qimin Zhan Jie Chen;Yan Wang;Di Zhao;Lingyuan Zhang;Weimin Zhang;Jiawen Fan;Jinting Li;Qimin Zhan

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.