Zinc-Transporting Protein ZIP4 Drives Aggressive Growth in Glioblastoma Brain Tumors

Recent research has shed new light on why glioblastoma, the deadliest form of brain cancer, is so aggressively difficult to treat. A study published in the Proceedings of the National Academy of Sciences and led by University of Oklahoma scientists identifies the zinc-transporting protein ZIP4 as a major contributor to tumor growth.

Normally, ZIP4 helps regulate and transport zinc throughout the body, which is essential for good health. However, scientists found that in the context of glioblastoma, ZIP4 behaves differently—triggering a series of events that fuel tumor progression. Glioblastoma cells absorb about ten times more zinc than normal brain tissue, allowing the tumor to thrive.

Researchers discovered that high ZIP4 levels cause glioblastoma to release small, bubble-like structures known as extracellular vesicles (EVs). These EVs contain another protein called TREM1, which typically helps the immune system fight infection. In glioblastoma, however, TREM1 instead reprograms nearby immune cells called microglia. Rather than attacking the tumor, these microglia are manipulated to support tumor growth by releasing chemicals that promote further tumor expansion.

This new understanding of ZIP4's function in brain cancer opens potential avenues for developing targeted treatments that could disrupt this harmful zinc transport mechanism. By interrupting these zinc-driven signals, future therapies may be able to slow or prevent the rapid growth characteristic of glioblastoma, giving hope for improved outcomes in this challenging disease.