YAP Mediates Tumorigenesis in Neurofibromatosis Type 2 by Promoting Cell Survival and Proliferation through a COX-2–EGFR Signaling Axis
| Autor: | Anat Stemmer-Rachamimov, Smitha Kota, William Guerrant, Vinay Mandati, Joseph L. Kissil, Mohammad Fallahi, Scott Troutman |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Neurofibromatosis 2 Cancer Research medicine.medical_specialty Carcinogenesis Cell Survival Cell Schwann cell Biology medicine.disease_cause Amphiregulin Article 03 medical and health sciences Internal medicine medicine Humans Prostaglandin E2 Transcription factor Cells Cultured Adaptor Proteins Signal Transducing Cell Proliferation Cell growth Signal transducing adaptor protein YAP-Signaling Proteins Phosphoproteins ErbB Receptors 030104 developmental biology Endocrinology medicine.anatomical_structure Oncology Cyclooxygenase 2 Cancer research Schwann Cells Signal Transduction Transcription Factors medicine.drug |
| Zdroj: | Cancer Research. 76:3507-3519 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | The Hippo–YAP pathway has emerged as a major driver of tumorigenesis in many human cancers. YAP is a transcriptional coactivator and while details of YAP regulation are quickly emerging, it remains unknown what downstream targets are critical for the oncogenic functions of YAP. To determine the mechanisms involved and to identify disease-relevant targets, we examined the role of YAP in neurofibromatosis type 2 (NF2) using cell and animal models. We found that YAP function is required for NF2-null Schwann cell survival, proliferation, and tumor growth in vivo. Moreover, YAP promotes transcription of several targets including PTGS2, which codes for COX-2, a key enzyme in prostaglandin biosynthesis, and AREG, which codes for the EGFR ligand, amphiregulin. Both AREG and prostaglandin E2 converge to activate signaling through EGFR. Importantly, treatment with the COX-2 inhibitor celecoxib significantly inhibited the growth of NF2-null Schwann cells and tumor growth in a mouse model of NF2. Cancer Res; 76(12); 3507–19. ©2016 AACR. |
| Databáze: | OpenAIRE |
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