ReferenceID 3565
YAP Suppresses Lung Squamous Cell Carcinoma Progression via Deregulation of the DNp63-GPX2 Axis and ROS Accumulation
Cancer Res
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 f
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Record Fields
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- Reference Id
- 3565
- Evidence Id
- 20155
- Core Evidence Id
- 20155
- Source Reference Id
- 433
- Herb2 Reference Id
- HBREF000753
- Subject Paper Key
- HBIN023784_28916653
- Pubmed Id
- 28916653
- Doi
- 10.1158/0008-5472.CAN-17-0449
- Paper Title
- YAP Suppresses Lung Squamous Cell Carcinoma Progression via Deregulation of the DNp63-GPX2 Axis and ROS Accumulation
- Paper 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.
- Journal
- Cancer Res
- Publish Year
- 2017
- Experiment Subject
- patient-derived xenograft models
- Experiment Type
- Cell Experiment
- Phenotype Related
- Lung Squamous Cell Carcinoma
- Paper Title Cn
- Paper Title En
- YAP Suppresses Lung Squamous Cell Carcinoma Progression via Deregulation of the DNp63-GPX2 Axis and ROS Accumulation
- Bilingual Status
- semi_complete