ORCID
- Parkinson, David: 0000-0002-5704-4923
Abstract
Schwannoma tumours typically arise on the eighth cranial nerve and are mostly caused by loss of the tumour suppressor Merlin (NF2). There are no approved chemotherapies for these tumours and the surgical removal of the tumour carries a high risk of damage to the eighth or other close cranial nerve tissue. New treatments for schwannoma and other NF2-null tumours such as meningioma are urgently required. Using a combination of human primary tumour cells and mouse models of schwannoma, we have examined the role of the Hippo signalling pathway in driving tumour cell growth. Using both genetic ablation of the Hippo effectors YAP and TAZ as well as novel TEAD palmitoylation inhibitors, we show that Hippo signalling may be successfully targeted in vitro and in vivo to both block and, remarkably, regress schwannoma tumour growth. In particular, successful use of TEAD palmitoylation inhibitors in a preclinical mouse model of schwannoma points to their potential future clinical use. We also identify the cancer stem cell marker aldehyde dehydrogenase 1A1 (ALDH1A1) as a Hippo signalling target, driven by the TAZ protein in human and mouse NF2-null schwannoma cells, as well as in NF2-null meningioma cells, and examine the potential future role of this new target in halting schwannoma and meningioma tumour growth.
DOI
10.1093/brain/awac342
Publication Date
2022-09-23
Publication Title
Brain
ISSN
0006-8950
Embargo Period
2022-11-08
Organisational Unit
Peninsula Medical School
Recommended Citation
Parkinson, D. B. (2022) 'Inhibition of YAP/TAZ-driven TEAD activity prevents growth of NF2-null schwannoma and meningioma', Brain, . Available at: https://doi.org/10.1093/brain/awac342