Principal Investigators: 

Dr Henning Wackerhage

Institution: 
Award Amount: 
£24,080
Duration: 
2 years

This project is investigating the role of a gene called ‘TAZ’ in rhabdomyosarcoma, looking at how TAZ can be used in diagnosis, how it effects treatment, and if it can be used as a future drug target.  It has the potential to improve both the diagnosis and treatment of patients with rhabdomyosarcoma.

TAZ & rhabdomyosarcoma (RMS): TAZ expression in human samples, TAZ transformation of myoblasts and YAP/TAZ drug discovery

This project is based at the University of Aberdeen, but will involve collaborators from London (Institute of Cancer Research) and as far afield as Switzerland (Swiss Institute of Bioinformatics). Rhabdomyosarcomas are cancers where cells resemble dividing muscle cells. These cancers are aggressive and occur mainly in children. In this project, Dr Wackerhage and his team will study a gene called TAZ that they have found to be highly active in rhabdomyosarcomas.

During the project, the team will study various aspects of the relationship between TAZ and rhabdomyosarcoma, including:

  • Whether high levels of TAZ mark certain types of rhabdomyosarcoma. If this is the case it could lead to better diagnosis of patients with rhabdomyosarcoma.
  • Whether high levels of TAZ make cells resistant to chemotherapy, and whether lowering the levels of TAZ turns rhabdomyosarcoma cells into less cancer-like cells
  • Whether increasing the levels of TAZ in normal muscle cells leads to the formation of rhabdomyosarcoma-like cells

For the last stage, they will screen around 300 natural compounds to search for compounds that will inhibit this gene (TAZ), as such compounds could be future drugs to treat rhabdomyosarcoma patients. Further, they will develop assays (experimental procedures) that can be used in future to test for drugs that may inhibit TAZ and YAP (another gene found in rhabdomyosarcomas) and so could be used to treat rhabdomyosarcoma.

Potential impact:

  • More accurate diagnosis of rhabdomyosarcoma
  • A better understanding of the role of TAZ in rhabdomyosarcoma
  • The discovery of compounds that inhibit TAZ, and could therefore be used to make future drugs to treat rhabdomyosarcoma
  • Developing techniques to screen for drugs that could potentially be used to treat rhabdomyosarcoma

Outputs

Publications

  • Wackerhage, H. et al. (2014) The Hippo signal transduction network in skeletal and cardiac muscle. Science Signalling 7(337). Read more: https://www.ncbi.nlm.nih.gov/pubmed/25097035
  • Tremblay, A. M. et al. (2014) The Hippo transducer YAP1 transforms activated satellite cells and is a potent effector of embryonal rhabdomyosarcoma formation. Cancer Cell 26(2). Read mor:: https://www.ncbi.nlm.nih.gov/pubmed/25087979
  • Mohamed, A. D., Tremblay, A. M., Muray, G. I. and Wackerhage, H. (2015) The Hippo signal transduction pathway in soft tissue sarcomas. Biochimica et Biophysica acta, 1856(1). Read more: https://www.ncbi.nlm.nih.gov/pubmed/26050962
  • Mohamed, A. D. et al. (2016) The Hippo effector TAZ (WWTR1) transforms myoblasts and TAZ abundance in associated with reduced survival in embryonal rhabdomyosarcoma. The Journal of Pathology 240(1). Read more: https://www.ncbi.nlm.nih.gov/pubmed/27184927

Publications & Workshops

  • When Hippo met MCAT: How Hippo links to stem cells, cancer and dystrophy in skeletal muscle. Presentation given at the Nineth Cancer Colloquium at St Andrews. February, 2014. Scotland, UK.
  • The Role of the Hippo Pathway in Rhabdomyosarcoma. Presentation given at the Scottish Sarcoma Network meeting. May, 2015. Dundee, UK.
  • Taz and Yap in rhabdomyosarcoma: agonist or antagonist? Presentation given at the Zurich Rhabdomyosarcoma meeting. July, 2014. Zurich, Switzerland.
  • Persistent YAP hyperactivity drives CINSARC gene expression and results in tumours with complex genomes. Presentation given at the Keystone Symposia into The Hippo Pathway: Signalling, Development and Disease. May, 2015. New Mexico, USA.
  • Wackerhage, H. Presentation given at the Oxford Hippo Meeting. 2015.

Further Funding

  • Further funding of £9,870 secured from the Friends of Anchor for Wackerhage H, Stevenson D, Turbitt J, Urcia, R.’s project entitled: Does the Yap oncogene worsen cancer by inducing chromosomal instability and oncogene copy number gains? 2014.
Project status: 
completed