Prostate cancer (PCa) is one of the most prevalent cancer in males. Although the majority of the patients can benefit from the present clinical treatments, 20%-30% of the patients who originally... Show moreProstate cancer (PCa) is one of the most prevalent cancer in males. Although the majority of the patients can benefit from the present clinical treatments, 20%-30% of the patients who originally respond to the therapy still develop incurable, castration-resistance bone metastases, which is a main cause of death in PCa . In this thesis, I combined an advanced zebrafish xenograft model with in vitro cellular approaches and mice xenografts to study the early stage of PCa metastasis. Using this comprehensive esearch platform, I identified multiple key signaling pathways that play essential roles in promoting the onset of PCa metastatis. The pathways I discovered include Cripto-associated EMT plasticity, CDC-42-N-Wasp-Cortactin associated mechanosensing and mechanotransduction, microenvironment dependent NF-ĸB-Activin A signaling pathway, and AMPK-Autophagy dependent metabolic stress coping pathway. Show less
Vertebrates, especially mammals, have long been used as research models in the study of human diseases. During this research we have demonstrated the usefulness of a relatively new animal model,... Show moreVertebrates, especially mammals, have long been used as research models in the study of human diseases. During this research we have demonstrated the usefulness of a relatively new animal model, the zebrafish, in understanding human disease formation, progression and even treatment. We first analysed the impact that exposure to constant chronic hypoxia has in the zebrafish heart, both at the morphological and genetic levels. On chapters three and four we demonstrated the worth of the zebrafish larvae in understanding metastasis formation and progression. Whereas in chapter three we focused on the use of the zebrafish as a model to rapidly test the metastatic behaviour of human pancreatic cancer cell lines and primary human tumours; on chapter four we researched the role of retinoic acid receptor antagonist, and mir10-a, as a potential new anti-cancer therapy for pancreatic adenocarcinoma. Show less
