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.
Keywords: ILK; LFG-500; YAP; epithelial–mesenchymal transition; metastasis.
© 2021. The Author(s), under exclusive licence to CPS and SIMM.