Understanding the role of receptor tyrosine kinase in Glioblastoma using Drosophila Melanogaster model system

Understanding the role of receptor tyrosine kinase in Glioblastoma using Drosophila Melanogaster model system

Presenter(s)

Minh T Ho, Kirti Snigdha

Description

Glioblastoma Multiforme (GBM) is one the most aggressive form and lethal form of brain tumors. Every year thousands of new cases are reported with a very poor prognosis. High lethality of GBM can be attributed to its recurrence after treatment, cause of which is currently unknown. Recent studies have identified few key signaling pathway components which are modified in the GBM. . These transmembrane proteins are apical of several interconnected signaling cascades. Phosphatidylinositol 3-kinase-mammalian target of rapamycin (PI3K/mTOR) signaling is elevated in ~88% of all glioblastoma due to suppression of PTEN. It is predicted that PI3K signaling contributes to therapy resistance in GBM cell lines due to its role in motility and proliferation. Along with the activated RAS from mitogen-activated protein kinase (MAPK) pathway , PI3K-mTOR signaling pathways control cell survival, differentiation, proliferation, metabolism, and motility in response to extracellular cues. Overexpression of activated RAS has been reported in multiple cases of GBM. Growth factor receptors that regulate RAS like Receptor tyrosine kinases are also often overexpressed by mutations in many different cancers, including glioblastoma. We hypothesize that receptor tyrosine kinases (RTK) affect the GBM growth by interacting with PI3K/mTOR and RAS/MAPK pathway and could be a possible target for GBM therapy. Since most of the signaling pathways are conserved from flies to mammals we have created a simple glioma model in Drosophila melanogaster to study this interaction. We generated the glioblastoma model by suppressing Pten while overexpressing oncogene RasV12 in glial cells of the fly brain to induce tumor. Flies with genotype UASPtenRNAi UASRasV12; Repo Gal4 UASGFP developed aggressive brain tumors and failed to survive to the adult stage. We will downregulate receptor tyrosine kinases like ALK and SEV in this glioblastoma model and evaluate its effect on growth and repopulation of glioblastoma. Here we report our recent findings.

Publication Date

4-5-2017

Project Designation

Independent Research - Graduate

Primary Advisor

Madhuri Kango-Singh

Primary Advisor's Department

Biology

Keywords

Stander Symposium project

Understanding the role of receptor tyrosine kinase in Glioblastoma using Drosophila Melanogaster model system

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