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胡国宏

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期刊论文

YAP Suppresses Lung Squamous Cell Carcinoma Progression via Deregulation of the DNp63–GPX2 Axis and ROS Accumulation

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Cancer Res,2017,77(21):5769–81 | 2017年11月01日 | 10.1158/0008-5472.CAN-17-0449

URL:https://cancerres.aacrjournals.org/content/77/21/5769

摘要/描述

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.

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【免责声明】以下全部内容由[胡国宏]上传于[2020年10月16日 13时58分11秒],版权归原创者所有。本文仅代表作者本人观点,与本网站无关。本网站对文中陈述、观点判断保持中立,不对所包含内容的准确性、可靠性或完整性提供任何明示或暗示的保证。请读者仅作参考,并请自行承担全部责任。

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