Investigation of the Genetic Interactions between Hippo Signaling Pathway and Drosophila C-terminal Src kinase (dCsk)
The focus of my research revolved around the intersection between the Hippo tumor suppressor pathway and the Src oncogenic pathway. Both pathways control tissue and organ size during development by regulating cell proliferation, cell death, cell migration, and cell adhesion. Aberrant functions in either pathway are often detected in human cancers and correlate with poor prognosis. The Drosophila C-terminal Src kinase (dCsk) is a genetic modifier of warts (wts), a tumor-suppressor gene in the Hippo pathway, and interacts with the Src oncogene. Reduction in dCsk expression and the consequent activation of Src are reported in hepatocellular and colorectal tumors. Previous studies show that dCsk regulates cell proliferation and tissue size during development. Given the similarity in the loss-of-function phenotypes of dCsk and wts, we investigated the interactions of dCsk with the Hippo pathway components. We tested if loss of dCsk resulted in changes in activity levels of Hippo pathway target Yki, and if dCsk and Hippo pathway genes genetically interact. We found multiple lines of evidence suggesting that loss of dCsk using RNAi mediated elimination of dCsk in large patches of cells causes overgrowth due to increased proliferation, due to increased Yki activity. The effects of loss of dCsk are cell autonomous, and our results of epistasis experiments of dCsk and Hippo pathway components place dCsk between Dachs and Zyx that function downstream of Fat in the Hippo network. Hence we concluded that dCsk regulates growth via the Hippo signaling pathway.
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Biology | Life Sciences
Kwon, Hailey Jimin, "Investigation of the Genetic Interactions between Hippo Signaling Pathway and Drosophila C-terminal Src kinase (dCsk)" (2015). Honors Theses. 69.