Partnership for the Advancement of Cancer Research: NMSU & FHCRC (1 of 2)Full Project #7: Genetic analysis of Egfr signaling and cell adhesionJennifer Curtiss (NMSU) / Bruce Edgar (FHCRC)ABSTRACTWhether or not metastasis occurs can make the difference between life and death for a cancer patient, andwhether or not a cancer cell metastasizes lies in its ability and propensity to adhere to other cells. Thepresence and activity of the cell adhesion molecule E-cadherin in adherens junctions is required for integrity ofepithelia, and its regulation is critical for morphogenesis of epithelial-derived structures. Little wonder thatunregulated E-cadherin activity has been implicated in development and progression of highly malignantinvasive carcinomas. But what regulates E-cadherin expression and activity? We have discovered that theEpidermal Growth Factor Receptor (Egfr) signaling pathway, which is also associated with cancer cell invasion,regulates expression of E-cadherin and differential cell affinity in two Drosophila epithelia, the wing and eyeantennalimaginal discs. Furthermore, Egfr signaling and E-cadherin function have interrelated functions in themorphogenesis of structures such as the wing veins and ommatidia, which are derived from the wing and eyediscs, respectively. The small molecule GTPase Rap1 also affects E-cadherin localization and thedifferentiation of Egfr-dependent cell types during both wing and eye development. In an effort to elucidate therelationships between Egfr, Rap1 and E-cadherin, we will use loss- and gain-of-function approaches todetermine what role Rap1 plays in the developing wing and eye imaginal discs. We will also use a mutationbasedapproach to explore the effect of E-cadherin-mediated adhesion on Egfr signaling. We will use Rap1gain-of-function phenotypes to screen for genes involved in controlling E-cadherin. Finally, we will use amicroarray-based strategy to identify transcriptional targets of the Egfr signaling pathway and Rap1. Theremarkable similarities between Drosophila and vertebrates in these developmental processes suggest thatour discoveries will lead to new tactics in the fight against cancer.
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