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Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice
Published on: December 21, 2019
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Targeting YAP in malignant pleural mesothelioma
Wen-Qian Zhang1,2, Yu-Yuan Dai1, Ping-Chih Hsu1,3
1Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
Journal of Cellular and Molecular Medicine
|May 5, 2017
Summary
Targeting Yes-associated protein (YAP) shows promise for treating malignant mesothelioma. Inhibiting YAP with verteporfin or siRNA reduced cancer cell activity and invasion, suggesting YAP as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Malignant mesothelioma is an aggressive cancer with poor prognosis.
- Elevated Yes-associated protein (YAP) activity is linked to mesothelioma's poor prognosis.
Purpose of the Study:
- To evaluate the therapeutic potential of targeting YAP in malignant mesothelioma.
- To investigate the role of YAP signaling in mesothelioma cell proliferation, invasion, and tumor formation.
Main Methods:
- Assessed YAP activity in mesothelioma cell lines and a normal mesothelial cell line.
- Treated cell lines with the YAP/TEAD inhibitor verteporfin and YAP-targeting siRNA.
- Analyzed YAP protein levels, downstream gene expression, and GTIIC reporter activity.
- Evaluated effects on cell invasion and tumorsphere formation.
- Investigated the role of Rho/ROCK signaling in YAP activation.
Main Results:
- Malignant mesothelioma cell lines exhibited increased YAP activity compared to normal cells.
- Verteporfin and siRNA-mediated YAP inhibition significantly reduced YAP activity, invasion, and tumorsphere formation.
- YAP overexpression rescued cell viability and reporter activity after YAP inhibition.
- ROCK2 inhibition decreased YAP activity, suggesting Rho/ROCK signaling contributes to YAP activation.
Conclusions:
- YAP is a potential therapeutic target for malignant mesothelioma.
- Targeting YAP signaling pathways offers a promising strategy for mesothelioma treatment.
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