期刊
ACTA PHARMACOLOGICA SINICA
卷 42, 期 11, 页码 1847-1859出版社
NATURE PUBL GROUP
DOI: 10.1038/s41401-021-00655-y
关键词
epithelial– mesenchymal transition; metastasis; LFG-500; YAP; ILK
资金
- National Natural Science Foundation of China [81402969, 81973341]
- Six Talent Peaks Project in Jiangsu Province [2017-SWYY-075]
- Science and Technology Program of Guangzhou [202002030010]
- Fundamental Research Funds for the Central Universities [21620426]
- Science and Technology Innovation Promoting Project of Xuzhou [KC20066]
- National Demonstration Center for Experimental Basic Medical Science Education (Xuzhou Medical University)
- 333 High-level Talents Project of Jiangsu Province
The study showed that LFG-500 can inhibit EMT-associated migration and invasion in breast cancer and lung adenocarcinoma cell lines by downregulating YAP activity. Further research indicated that the suppression of YAP activation induced by LGF-500 is mediated by ILK.
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-beta)-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据