Usage Information
Schwannoma development is mediated by Hippo pathway dysregulation and modified by RAS/MAPK signaling
Abstract
Schwannomas are tumors of the Schwann cells that cause chronic pain, numbness, and potentially life-threatening impairment of vital organs. Despite the identification of causative genes, including NF2 (Merlin), INI1/SMARCB1, and LZTR1, the exact molecular mechanism of schwannoma development is still poorly understood. Several studies have identified Merlin as a key regulator of the Hippo, MAPK, and PI3K signaling pathways; however, definitive evidence demonstrating the importance of these pathways in schwannoma pathogenesis is absent. Here, we provide direct genetic evidence that dysregulation of the Hippo pathway in the Schwann cell lineage causes development of multiple schwannomas in mice. We found that canonical Hippo signaling through the effectors YAP/TAZ is required for schwannomagenesis and that MAPK signaling modifies schwannoma formation. Furthermore, cotargeting YAP/TAZ transcriptional activity and MAPK signaling demonstrated a synergistic therapeutic effect on schwannomas. Our new model provides a tractable platform to dissect the molecular mechanisms underpinning schwannoma formation and the role of combinatorial targeted therapy in schwannoma treatment.
Authors
Zhiguo Chen, Stephen Li, Juan Mo, Eric Hawley, Yong Wang, Yongzheng He, Jean-Philippe Brosseau, Tracey Shipman, D. Wade Clapp, Thomas J. Carroll, Lu Q. Le
Usage data is cumulative from August 2025 through August 2026.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 2,513 | 236 |
| 321 | 53 | |
| Figure | 984 | 3 |
| Supplemental data | 148 | 6 |
| Citation downloads | 390 | 0 |
| Totals | 4,356 | 298 |
| Total Views | 4,654 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
