Role of Epidermal Growth Factor-Triggered PI3K/Akt Signaling in the Migration of Medulloblastoma-Derived Cells
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Medulloblastoma (MB) is the most common brain cancer diagnosed among children. The cellular pathways that regulate MB invasion in response to environmental cues remain incompletely understood. Herein, we examine the migratory response of human MB-derived Daoy cells to different concentration profiles of Epidermal Growth Factor (EGF) using a microfluidic system. Our findings provide the first quantitative evidence that EGF concentration gradients modulate the chemotaxis of MB-derived cells in a dose-dependent manner via the EGF receptor (EGF-R). Data illustrates that higher concentration gradients caused increased number of cells to migrate. In addition, our results show that EGF-induced receptor phosphorylation triggered the downstream activation of phosphoinositide-3 kinase (PI3K)/Akt pathway, while its downstream activation was inhibited by Tarceva (an EGF-R inhibitor), and Wortmannin (a PI3K inhibitor). The treatment with inhibitors also severely reduced the number of MB-derived cells that migrated towards increasing EGF concentration gradients. Our results provide evidence to bolster the development of anti-migratory therapies as viable strategies to impede EGF-stimulated MB dispersal.
KeywordsChemotaxis EGF microfluidics Daoy PI3K/Akt
This work has been supported by The National Institutes of Health (R21 CA 118255 and U54 MICHOR), The Pediatric Brain Tumor Foundation, and PSC-CUNY (No. 69424). The authors wish to thank Ms. Jennifer Rico for her technical assistance in this work.
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