Targeting the ILK/YAP axis by LFG-500 blocks epithelial–mesenchymal transition and metastasis  

作　　者：Cheng-lin Li Juan Li Shu-yuan Gong Meng Huang Rui Li Gui-xiang Xiong Fan Wang Qiu-ming Zou Qi Qi Xiao-xing Yin 

机构地区：[1]Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy,Xuzhou Medical University,Xuzhou 221004,China [2]MOE Key Laboratory of Tumor Molecular Biology,Clinical Translational Center for Targeted Drug,Department of Pharmacology,School of Medicine,Jinan University,Guangzhou 510632,China

出　　处：《Acta Pharmacologica Sinica》2021年第11期1847-1859,共13页中国药理学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(grant no.81402969 and 81973341);supported by the 333 High-level Talents Project of Jiangsu Province,the Six Talent Peaks Project in Jiangsu Province(grant no.2017-SWYY-075);the Science and Technology Program of Guangzhou(grant no.202002030010);the Fundamental Research Funds for the Central Universities(grant no.21620426);the Science and Technology Innovation Promoting Project of Xuzhou(grant no.KC20066);the National Demonstration Center for Experimental Basic Medical Science Education(Xuzhou Medical University).

摘　　要：Metastasis is the main cause of mortality in patients with cancer.Epithelial–mesenchymal transition(EMT),a crucial process in cancer metastasis,is an established target for antimetastatic drug development.LFG-500,a novel synthetic flavonoid,has been revealed as a potential antitumor agent owing to its various activities,including modulation of EMT in the inflammatory microenvironment.Here,using a transforming growth factor beta(TGF-β)-induced EMT models,we found that LFG-500 inhibited EMT-associated migration and invasion in human breast cancer,MCF-7,and lung adenocarcinoma,A549,cell lines,consistent with the observed downregulation of YAP activity.Further studies demonstrated that LGF-500-induced suppression of YAP activation was mediated by integrin-linked kinase(ILK),suggesting that the ILK/YAP axis might be feasible target for anti-EMT and antimetastatic treatments,which was verified by a correlation analysis with clinical data and tumor specimens.Hence,our data support the use of LGF-500 as an antimetastatic drug in cancer therapy and provide evidence that the ILK/YAP axis is a feasible biomarker of cancer progression and a promising target for repression of EMT and metastasis in cancer therapy.

关 键 词：epithelial-mesenchymal transition METASTASIS LFG-500 YAP ILK 

分 类 号：R730.5[医药卫生—肿瘤]