Overview

• Glioblastoma cells overexpress the zinc transporter ZIP4, leading to a tenfold increase in zinc uptake compared to normal brain tissue.
• ZIP4 overexpression triggers the release of extracellular vesicles (EVs) containing TREM1, which reprograms microglia to support tumor growth.
• Microglia altered by TREM1 release chemicals that enhance glioblastoma growth and progression.
• A dual small-molecule inhibitor targeting both ZIP4 and TREM1 has shown promise in preclinical tests, slowing tumor growth by blocking their actions.
• The findings, published in the Proceedings of the National Academy of Sciences, provide a framework for developing targeted therapies for glioblastoma, a highly aggressive brain cancer with limited treatment options.