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May 2, 2025 – Researchers at the University of Oklahoma have identified a crucial mechanism behind the aggressive growth of glioblastoma, the deadliest form of brain cancer. The findings, published this week in the Proceedings of the National Academy of Sciences, spotlight a zinc-transporting protein called ZIP4 as a key driver of tumor progression.
ZIP4: From Essential Function to Tumor Accelerator
Under normal circumstances, ZIP4 helps maintain healthy zinc levels in the body. However, the new study reveals that in glioblastoma, ZIP4 is overexpressed, causing the tumor to absorb about ten times more zinc than normal brain tissue. This excess zinc intake sets off a chain reaction that fuels tumor growth.
“Everything starts with the fact that ZIP4 is overexpressed in glioblastoma,” explained Dr. Min Li, the study’s senior author and professor at the University of Oklahoma College of Medicine. “That triggers all these downstream events that help the tumor to grow.”
How ZIP4 Drives Tumor Growth
The research team discovered that glioblastoma cells with high levels of ZIP4 release tiny, bubble-like structures called extracellular vesicles (EVs). These vesicles carry a protein known as TREM1, which typically helps the immune system combat infections. In the context of glioblastoma, however, TREM1 reprograms nearby brain immune cells (microglia), turning them into supporters of tumor growth. The altered microglia then secrete chemicals that further promote the tumor’s expansion.
Promising Avenues for Treatment
In laboratory tests, the researchers used a small-molecule inhibitor designed to target both ZIP4 and TREM1. The inhibitor successfully attached to the proteins, blocking their actions and slowing tumor growth. “This tells us that ZIP4 and TREM1 may be promising therapeutic targets,” said Dr. Li.
Dr. Ian Dunn, a neurosurgeon and executive dean at the OU College of Medicine who co-authored the study, highlighted the significance of the findings: “These results are really exciting in such a debilitating cancer. The hope and promise is to translate these findings to novel treatment approaches to improve the lives of our patients.”
Building on Previous Research
While this is Dr. Li’s first major publication on glioblastoma, his previous work has demonstrated that ZIP4 also plays a role in pancreatic cancer, making tumor cells more resistant to chemotherapy and enabling them to spread to other organs. This new research suggests ZIP4 could be a common target in multiple aggressive cancers.
What’s Next?
With a median survival rate of just 14 months for glioblastoma patients, new treatment strategies are urgently needed. The identification of ZIP4 and TREM1 as potential therapeutic targets offers hope for more effective interventions in the future.
Disclaimer:
This article summarizes recent scientific research and is intended for informational purposes only. The findings discussed are based on laboratory studies and are not yet available as approved treatments. Patients should consult healthcare professionals for medical advice and should not alter their treatment plans based on this report. For more details, refer to the original publication:
Liyang Zhang et al, A zinc transporter drives glioblastoma progression via extracellular vesicles-reprogrammed microglial plasticity, Proceedings of the National Academy of Sciences (2025). Read the study
