An Investigation Into the Molecular Mechanisms and Genes Involved in Hypoxic Signalling Pathways in Neural Crest Derived Tumours

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Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
Griffith Health
Hypoxia-inducing factors (HIF’s) are master regulators of metastasis in most solid tumours because of their ability to cause rapid cell proliferation, glycolytic metabolism, angiogenesis, and tumour invasiveness. Considerable progress has been made in defining HIF function in many hallmarks of carcinogenesis, including primary and metastatic tumour aggressiveness, poor prognosis, radio and chemotherapeutic resistance, vascular remodelling, inflammation, and hypoxia/ischemia induced cell damage. Hypoxic activation of HIF’s is gaining prominence in many cancer types as an essential mediator of malignant progression to metastasis. However, in neuroendocrine tumours of neural crest origin, hypoxia is often associated with dysfunction in genes encoding key enzymes of the TCA cycle leading to abnormally high levels of particular metabolites such as succinate that cause HIF stabilization.