| Literature DB >> 28916653 |
Hsinyi Huang1,2,3, Wenjing Zhang4,2,3, Yafang Pan1,2,3,5, Yijun Gao1,2,3, Lei Deng6, Fuming Li1,2,3, Fei Li1,2,3, Xueyan Ma1,2,3, Shenda Hou1,2,3, Jing Xu7, Peixue Li1,2,3, Xiaoxun Li8, Guohong Hu8, Cheng Li9, Haiquan Chen10, Lei Zhang1,2,3,5, Hongbin Ji4,2,3,5.
Abstract
Lung squamous cell carcinoma (SCC), accounting for approximately 30% of non-small cell lung cancer, is often refractory to therapy. Screening a small-molecule library, we identified digitoxin as a high potency compound for suppressing human lung SCC growth in vitro and in vivo Mechanistic investigations revealed that digitoxin attenuated YAP phosphorylation and promoted YAP nuclear sequestration. YAP activation led to excessive accumulation of reactive oxygen species (ROS) by downregulating the antioxidant enzyme GPX2 in a manner related to p63 blockade. In patient-derived xenograft models, digitoxin treatment efficiently inhibited lung SCC progression in correlation with reduced expression of YAP. Collectively, our results highlight a novel tumor-suppressor function of YAP via downregulation of GPX2 and ROS accumulation, with potential implications to improve precision medicine of human lung SCC. Cancer Res; 77(21); 5769-81. ©2017 AACR. ©2017 American Association for Cancer Research.Entities:
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Year: 2017 PMID： 28916653 DOI： 10.1158/0008-5472.CAN-17-0449
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701