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Title: The Hippo effector TAZ in rhabdomyosarcoma
Author: Mohamed, Abdalla Ahmed Diaai
ISNI:       0000 0004 5918 0579
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2015
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Persistent hyperactivity of the Hippo effector YAP in activated but not quiescent satellite cells (muscle stem cells) can give rise to embryonal rhabdomyosarcoma (ERMS). Taz is a paralogue of Yap and both have similar functions in most cell types. However, one report has suggested that Taz can, unlike Yap, promote the differentiation of myoblasts into myotubes. To further characterise the role of Taz in the muscle lineage and rhabdomyosarcoma TAZ abundance and localisation in rhabdomyosarcoma tissue arrays were assessed to test for association with clinical outcome. Additionally, wildtype TAZ and constitutively active TAZ S89A pMSCV retroviral vectors were created to stably transduce C2C12 myoblasts testing for Taz function. In addition, anchorage independent soft agarose assay has been performed in order to assess the tumourigenic property of Taz in C2C12 myoblasts. The presence of TAZ staining in ERMS was significantly associated with poorer survival. TAZ S89A expression in comparison to empty vector (negative control) significantly increased the proliferation of C2C12 myoblasts in reduced foetal calf serum (FCS). TAZ S89A- expressing myoblasts were able to grow and to form more colonies than empty vector myoblasts. In marked contradiction to the pro-tumourigenic role of TAZ in C2C12 myoblasts, ectopic TAZ expression enhanced the differentiation of C2C12 myoblasts. These findings point out the complex and obscure role of TAZ in the muscle lineage. Collectively, these results suggest that TAZ staining is associated with poorer survival in ERMS and that TAZ can transform C2C12 myoblasts indicating a contextual role for TAZ in the muscle lineage.
Supervisor: Not available Sponsor: Sarcoma UK
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Rhabdomyosarcoma