TRPM7 maintains progenitor-like features of neuroblastoma cells: implications for metastasis formation

Oncotarget
Jeroen MiddelbeekFrank N van Leeuwen

Abstract

Neuroblastoma is an embryonal tumor derived from poorly differentiated neural crest cells. Current research is aimed at identifying the molecular mechanisms that maintain the progenitor state of neuroblastoma cells and to develop novel therapeutic strategies that induce neuroblastoma cell differentiation. Mechanisms controlling neural crest development are typically dysregulated during neuroblastoma progression, and provide an appealing starting point for drug target discovery. Transcriptional programs involved in neural crest development act as a context dependent gene regulatory network. In addition to BMP, Wnt and Notch signaling, activation of developmental gene expression programs depends on the physical characteristics of the tissue microenvironment. TRPM7, a mechanically regulated TRP channel with kinase activity, was previously found essential for embryogenesis and the maintenance of undifferentiated neural crest progenitors. Hence, we hypothesized that TRPM7 may preserve progenitor-like, metastatic features of neuroblastoma cells. Using multiple neuroblastoma cell models, we demonstrate that TRPM7 expression closely associates with the migratory and metastatic properties of neuroblastoma cells in vitro and in vivo. Mor...Continue Reading

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Methods Mentioned

BETA
delamination
transfection
FCS
PCR
xenograft
bioluminescence imaging
Assay

Software Mentioned

Image J
Webgestalt
ServiceXS
Living Image
ImageJ
Illumina GenomeStudio
Vennmaster
Multi Experiment Viewer
Gene Expression

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