English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Autocrine and paracrine factors, including glutamate and epidermal growth factor ( EGF ), are potent inducers of brain tumor cell invasion, a pathological hallmark of malignant gliomas. System xc(–) consists of  xCT  and  CD 98hc subunits and functions as a plasma membrane antiporter for the uptake of extracellular cystine in exchange for intracellular glutamate. We previously showed that the  EGF  receptor ( EGFR ) interacts with  xCT  and thereby promotes the activity of system xc(–) in a kinase‐independent manner, resulting in enhanced glutamate release in glioma cells. However, the molecular mechanism underlying  EGFR ‐mediated glioma progression in a glutamate‐rich microenvironment has remained unclear. Here we show that the GluN2B subunit of the  N ‐methyl‐ d ‐aspartate–sensitive glutamate receptor ( NMDAR ) is a substrate of  EGFR  in glioma cells. In response to  EGF  stimulation,  EGFR  phosphorylated the  COOH ‐terminal domain of GluN2B and thereby enhanced glutamate‐ NMDAR  signaling and consequent cell migration in  EGFR ‐overexpressing glioma cells. Treatment with the  NMDAR  inhibitor  MK ‐801 or the system xc(–) inhibitor sulfasalazine suppressed  EGF ‐elicited glioma cell migration. The administration of sulfasalazine and  MK ‐801 also synergistically suppressed the growth of subcutaneous tumors formed by  EGFR ‐overexpressing glioma cells. Furthermore, sh RNA ‐mediated knockdown of  xCT  and GluN2B cooperatively prolonged the survival of mice injected intracerebrally with such glioma cells. Our findings thus establish a central role for  EGFR  in the signaling crosstalk between  xCT  and GluN2B‐containing  NMDAR  in glioma cells.

cancer science

Epidermal growth factor receptor promotes glioma progression by regulating  xCT  and GluN2B‐containing  N ‐methyl‐ d ‐aspartate–sensitive glutamate receptor signaling