About the Project
Epithelioid Hemangioendothelioma (EHE) is a rare type of cancer that affects vascular cells. Ages at diagnosis range from childhood to elderly with a higher prevalence in women. At presentation, EHE tumours are found mostly in liver, lung and bones. However, EHE is very heterogeneous and may involve many other sites. EHE can be indolent but may evolve into an aggressive disease with widespread metastases. Most EHE cases (90%) are characterized by a t(1;3) chromosomal translocation resulting in a fusion protein between the TAZ transcription factor and the calmodulin-binding transcription activator 1 (CAMTA1). In a few EHE cases, a translocation resulting in the production of the YAP1-TFE3 fusion protein has been described. Of high significance, both TAZ and YAP are downstream effectors of the Hippo pathway, a highly conserved signalling pathway implicated in cell growth, proliferation and specification, but also in cancer.
Due to a lack of model systems to study this disease, we still have little understanding of the consequences of TAZ/YAP fusion protein expression on the biology of endothelial cells. In this project, we propose to use the in vitro differentiation of embryonic stem cells (ESCs) as a model system to determine how the expression of the TAZ-CAMTA1 fusion protein affects the biological characteristic of primary endothelial cells.
References
Antonescu, C.R., Le Loarer, F., Mosquera, J.M., Sboner, A., Zhang, L., Chen, C.L., Chen, H.W., Pathan, N., Krausz, T., Dickson, B.C., et al. (2013). Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma. Genes, chromosomes & cancer 52, 775-784.
Lilly, A.J., Mazan, A., Scott, D.A., Lacaud, G., and Kouskoff, V. (2017). SOX7 expression is critically required in FLK1-expressing cells for vasculogenesis and angiogenesis during mouse embryonic development. Mechanisms of development 146, 31-41.
Sardaro, A., Bardoscia, L., Petruzzelli, M.F., and Portaluri, M. (2014). Epithelioid hemangioendothelioma: an overview and update on a rare vascular tumor. Oncology reviews 8, 259.
Tanas, M.R., Sboner, A., Oliveira, A.M., Erickson-Johnson, M.R., Hespelt, J., Hanwright, P.J., Flanagan, J., Luo, Y., Fenwick, K., Natrajan, R., et al. (2011). Identification of a disease-defining gene fusion in epithelioid hemangioendothelioma. Science translational medicine 3, 98ra82.
Varelas, X. (2014). The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease. Development 141, 1614-1626
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