|Title:||The migration signalling molecule NEDD9 and glioblastoma|
|Authors:||Zhong, Jessie Ze Ci|
|Publisher:||University of Sydney.|
Paediatrics and Child Health.
Children's Hospital at Westmead Clinical School.
|Abstract:||Glioblastoma is a malignant brain tumour characterised by diffuse and extensive invasion of normal brain parenchyma. Despite technological advances in treatment, overall survival still averages 12-15 months. The docking protein NEDD9 promotes cell migration, invasion and metastasis in multiple cancers and is suggested to be a specific regulator of Rac-dependent mesenchymal, elongated phenotype. NEDD9 knockdown did not induce cell rounding, but suppressed both cell migration in collagen matrices and spheroid invasion in brain slices. To assess clinical relevance of NEDD9, glioblastoma tumours were examined and NEDD9, absent in normal adult brain, was found to be highly-expressed in 30% of glioblastomas. Although NEDD9 was co-expressed with Proneural subtype marker DLL3, and high DLL3 expression was associated with improved survival, NEDD9 expression did not correlate with survival and therefore, was not predictive of patient outcome. Following identification and investigation of novel binding partner CIN85 (a regulator of EGFR uptake and endosomal sorting), NEDD9 was observed to downregulate total EGFR levels and reduce downstream signalling, without effecting EGFR trafficking. Collectively, data presented in this thesis confirmed that NEDD9 promotes invasion of malignant glioma and revealed a novel function of NEDD9 in regulating the stability of EGFR protein and its downstream signalling networks.|
|Access Level:||Access is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.|
|Rights and Permissions:||The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.|
|Type of Work:||PhD Doctorate|
|Type of Publication:||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (University of Sydney Access only)|
|ZHONG Jessie - Final Thesis.pdf||Thesis||77.58 MB||Adobe PDF|
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