Role of Epidermal Growth Factor-Triggered PI3K/Akt Signaling in the Migration of Medulloblastoma-Derived Cells

Abstract

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.

MiR-330-Mediated Regulation of SH3GL2 Expression Enhances Malignant Behaviors of Glioblastoma Stem Cells by Activating ERK and PI3K/AKT Signaling Pathways

“…MAPKs are a superfamily of protein serine–threonine kinases including ERKs. In addition, previous study found that EGF-induced receptor phosphorylation triggered the activation of downstream PI3K/Akt pathway which resulted in the change of various biological effects [41], [42]. To further clarify the potential mechanisms in the SH3GL2-dependent regulation of malignant behavior of GSCs, the detection of ERK and PI3K/AKT activity was carried out by Western blot after the expression of miR-330 and SH3GL2 were changed.…”

Controlled microfluidics to examine growth-factor induced migration of neural progenitors in the Drosophila visual system

“…Experiments used our established microfluidic system, called the bridged μLane, whose design and operation has been described previously in greater detail (Able et al, 2012; Dudu et al, 2012; Kong et al, 2010; Rico-Varela et al, 2015). As shown in Fig.…”

Low Concentration Microenvironments Enhance the Migration of Neonatal Cells of Glial Lineage

“…The simulation revealed that the concentration distribution within the microchannel reached steady-state at t = 103 h, after which no changes in concentration with time were seen. Concentration gradients were obtained by calculating the change in concentration along the channel length as done previously 15 via Eq. (3): $$G=\frac{\partial C}{\partial x}$$ where G is gradient, C is concentration (ng/mL), and x (m) is distance.…”