Date of Completion
Jianzhong Yu, Jeanne McCaffery
Allied Health Sciences
Cancer cells are notorious for growing in an unrestricted manner without regard for environmental cues. Recently, Li et al. (2019) discovered headcase (hdc) functions by binding to the mTORC1 complex in the mTOR signaling pathway and preventing further signaling. Interestingly, under nutrient restricted (NR) conditions, cells with mutated hdc proteins proliferated more than cells with normal functioning hdc. It is well known that insulin signaling is downregulated under NR conditions, so a potential signaling pathway with insulin, PI3K, PDK1, Akt, PTEN, and hdc was created as a way to explain the link between hdc function and nutritional status. A Drosophila melanogaster model using UAS-Gal4-induced eye-specific insulin signaling downregulation and Flippase-FRT-derived mosaic expression of mutant hdc cells and GFP wildtype (WT) cells was created to test this hypothesis. The eye discs of the third instar larvae were dissected, and observed under a fluorescent microscope. Hdc mutant clone sizes were the same as WT clones under normal insulin signaling conditions. However, when insulin signaling was downregulated, hdc mutant clones did tend to amass more total area than WT clones. Due to variability in clone sizes within eye discs, inadequate clone sizes for comparison in some eye discs, and lack of sampling, these observations are not statistically proven. Thus, this insulin signaling pathway shows some potential to exist. Further data collection and improvements on the model need to be pursued in order to come to more concrete proof about the existence of this insulin signaling pathway.
George, Thomas, "Headcase Regulates Growth in Response to Nutritional Status Downstream of Insulin Signaling" (2022). Honors Scholar Theses. 876.