ERK Phosphorylation Regulates the Aml1/Runx1 Splice Variants and the TRP Channels Expression during the Differentiation of Glioma Stem Cell Lines
Copyright policy )ERK Phosphorylation Regulates the Aml1/Runx1 Splice Variants and the TRP Channels Expression during the Differentiation of Glioma Stem Cell Lines
The identification of cancer stem cells in brain tumors paved the way for new therapeutic approaches. Recently, a role for the transcriptional factor Runx1/Aml1 and the downstream ion channel genes in brain cancer development and progression has been suggested. This study aimed to explore the expression and the role of Runx1/Aml1, its Aml1b and Aml1c splice variants and the downstream TRPA1 and TRPV1 ion channels in undifferentiated and day-14 differentiated neural stem cells (NSCs and D-NSCs) and glioblastoma stem cells (GSCs and D-GSCs) lines with different proneural (PN) or mesenchymal (MES) phenotype. Gene and protein expression were evaluated by qRT-PCR, cytofluorimetric, western blot and confocal microscopy analyses. Moreover, by western blot, we observed that ERK phosphorylation enhances the Aml1b and Aml1c protein expression during glioma differentiation. Furthermore, the agonists of TRPA1 and TRPV1 channels stimulated apoptosis/necrosis in GSCs and D-GSCs as evaluated by Annexin V and PI staining and cytofluorimetric analysis. Finally, by qRT-PCR, the modulation of Wnt/β catenin, FGF, and TGFβ/SMAD signaling pathways in PN- and MES-GSCs was reported. Overall, our results provide new evidence regarding Runx1/Aml1 isoform overexpression and modulation in TRP channel expression during gliomagenesis, thus offering new directions for glioblastoma therapy.
- Roma Tre University Italy
- Sapienza University of Rome Italy
- Istituto Superiore di Sanità (Rome) Italy
- Ospedale di Macerata Italy
- University of Camerino Italy
neural differentiation, RNA Splicing, Down-Regulation, TRPV Cation Channels, Apoptosis, TRPA1, Article, Cell Line, Tumor, TRP channel, Nerve Growth Factor, Humans, Protein Isoforms, Acrolein, Phosphorylation, Extracellular Signal-Regulated MAP Kinases, TRPA1 Cation Channel, QH573-671, Brain Neoplasms, Cell Differentiation, Glioma, Aml1 splice variants, Up-Regulation, TRPV1, ERK, Core Binding Factor Alpha 2 Subunit, glioma stem cells, Neoplastic Stem Cells, Cytology, Signal Transduction
neural differentiation, RNA Splicing, Down-Regulation, TRPV Cation Channels, Apoptosis, TRPA1, Article, Cell Line, Tumor, TRP channel, Nerve Growth Factor, Humans, Protein Isoforms, Acrolein, Phosphorylation, Extracellular Signal-Regulated MAP Kinases, TRPA1 Cation Channel, QH573-671, Brain Neoplasms, Cell Differentiation, Glioma, Aml1 splice variants, Up-Regulation, TRPV1, ERK, Core Binding Factor Alpha 2 Subunit, glioma stem cells, Neoplastic Stem Cells, Cytology, Signal Transduction
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).12 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!