Protein kinases play a critical role in a number of cellular processes, including cell proliferation, differentiation and apoptosis. The REarranged during Transfection (RET) receptor tyrosine kinase plays important roles in regulating cellular proliferation, migration, and survival in the normal development of neural crest derived tissues. Furthermore, aberrant activation of RET, through oncogenic mutations or overexpression, can contribute to tumourigenesis, regional invasion, and metastasis of several human cancers. RET relocalisation plays a role in cancer invasion and metastasis. Unfortunately, the detailed understanding of RET's dynamic function and the importance of quantitative, spatial and time-dependent parameters regarding RET trafficking is lacking. As such, the ability to manipulate RET activity using light would result in temporal control of enzymatic activity, thus serving as a valuable approach to probe the RET trafficking, further our understanding of cell movement and invasion. Cells will be exposed to photoresponsive RET inhibitors that can be turned on and off with light. Their effects on RET trafficking will be monitored by imaging. The results of these studies will provide new insights into intracellular RET trafficking and its role in cancer, ultimately leading to new therapeutic targets and improved disease management.
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