PgmNr D1099: Elucidating the role of various signaling pathways in lgl derived tumors in Drosophila egg chambers.

Authors:
Deeptiman Chatterjee; Wu-min Deng


Institutes
Florida State University, Tallahassee, FL.


Keyword: tumor suppressors and oncogenes

Abstract:

Major signaling pathways have been conserved between Drosophila and humans, making the former a good model organism for cancer research. Loss of polarity and tissue organization being one of the prominent characteristics of epithelial-derived cancers, it has been widely studied in Drosophila. Some of the first apical-basal polarity genes that regulate tissue organization have been studied in Drosophila egg chambers, the spatiotemporal development of which is quite well characterized. Many of these genes act as tumor suppressors in the epithelial follicle cells as they maintain the polarity and prevent defective overgrowth in the epithelia. One such tumor suppressor is the lethal Giant Larvae or lgl, a polarity-determining gene that works in consort with others such as dlg and scrib to characterize the basolateral region of the epithelial cell. Loss of lgl function results in rampant loss in polarity and an overgrowth phenotype. The spatiotemporal dynamism of follicular epithelia provides a unique opportunity to elucidate how various signaling pathways, namely the JAK-STAT, JNK, Hippo and Notch, act with each other to promote overgrowth and metastasis in lgl-derived tumors. Using various cell signaling reporters, antibody staining and tissue-specific Gal4 drivers to knockdown gene expression, we have found growth-promoting roles of JAK-STAT and JNK pathways in lgl tumors. We have also found that while the Hippo pathway is important in promoting Notch signaling in the regulation of cell differentiation and growth, its disruption causes a loss of polarity in the epithelia. We have also investigated the role of the Hippo and Notch pathways in causing overgrowth phenotype in Drosophila..



Flybase Genetic Index:
1. FlyBase gene symbol: l(2)gl; FBgn: FBgn0002121