Dataset Information

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.

SUBMITTER: Dudu V

PROVIDER: S-EPMC3832994 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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

Dudu Veronica V Able Richard A RA Rotari Veronica V Kong Qingjun Q Vazquez Maribel M

Cellular and molecular bioengineering 20121201 4

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 d ...[more]

PMID: 24273611

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Project description:When skin tissue is damaged, the wound microenvironment is hypoxic or anoxic due to the rupture of blood vessels and the high oxygen consumption of related cells; so far, it is not clear whether such hypoxic microenvironment will promote epidermal cell migration and the underlying molecular regulatory mechanisms of this effect remains unclear. Studies to date have shown that, immortal keratinocyte cell line HaCaT and primary human keratinocytes are maintained under conditions of hypoxia (1% oxygen) or normoxia. The researchers would adopt methods such as live cell imaging system, Western blotting, transwell assays and wound scratch assays etc. to study the changes of cell migration. Expression profile of mRNAs in HaCaT cells from 3 hypoxia and 3 normoxic conditions were analyzed by the Clariom D microarray assay. Gene Ontology (GO) and KEGG genomics analyses were performed to identify significant functions, pathways, and the associations of differentially expressed mRNAs. Moreover, the potential mechanism is discussed and studied. According to relevant results, the epidermal cell migration is promoted in the early hypoxia. Furthermore, experiment showed that 1456 mRNAs showed differential expression between the hypoxia and normoxic conditions, which included 537 upregulated and 919 downregulated mRNAs. These results also shown that all G proteins are upregulated. At the same time, GO analysis indicated that most upregulated mRNA are in connection with cell inflammation and migration. Pathway analysis indicated that 20 pathways corresponded to the upregulated mRNA and 6 pathways corresponded to the upregulated mRNA. These pathway analyses have indicated that genes involved in inflammation, migration and PI3K-Akt signaling are potentially regulated. Combine with microarray assay, we further shown that G protein accelerates epidermal cell migration via activation of PI3K/Akt-dependent mTORC1 signaling under the condition of hypoxia. Based on this evidence, researchers can further reveal the molecular and cellular mechanisms of local wound hypoxia, and for improving the wound healing.

Dataset Information

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

Publications

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

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