Georgetown Scientists Discover Hidden Role of Ezrin Protein as Dual Driver of Lethal Bone Cancer Metastasis

Georgetown researchers find that the "closed" form of ezrin protein binds to RNA to drive bone cancer spread, opening new doors for pediatric cancer treatment.

By: AXL Media

Published: Mar 18, 2026, 9:02 AM EDT

Source: Information for this report was sourced from Georgetown University Medical Center

Overturning Decades of Scientific Assumption Regarding Ezrin Protein Activity

A major study published in the journal Science Signaling has revealed a previously unknown dual function for the cancer associated protein ezrin, offering a new perspective on how osteosarcoma spreads. For decades, the scientific community believed that ezrin only influenced cancer when in its "open" state at the cell membrane, while its "closed" form within the cell’s interior was considered dormant. Researchers at Georgetown University’s Lombardi Comprehensive Cancer Center have now demonstrated that this closed form is a highly active RNA binding protein. By revealing that ezrin is active in both states, the study explains why this protein has been such a persistent and powerful driver of metastasis in bone cancer and other ezrin dependent tumors.

Innovative Zebrafish Models Identify the Mechanisms of Cancer Spread

To isolate the functions of the two different protein states, the research team utilized sophisticated genetic techniques in zebrafish models. Because ezrin naturally pivots between open and closed conformations, studying them in isolation had historically been impossible. Dr. Aykut Üren and his colleagues created osteosarcoma cells entirely devoid of ezrin and implanted them into zebrafish before reintroducing mutant forms of the protein locked into either the open or closed state. These experiments proved that even when locked in the supposedly inactive closed state, the protein was capable of restoring metastatic behavior in cancer cells, fundamentally changing the understanding of how these tumors navigate and colonize new tissues.

The Role of RNA Binding in Fueling Metastatic Behavior

The study’s most significant biochemical discovery is that the closed form of ezrin binds directly to RNA, influencing how genes are translated into the proteins that support tumor growth. This internal activity allows the cancer to maintain its aggressive profile from within the cell, rather than just through membrane interactions. Approximately 1,000 new cases of osteosarcoma are diagnosed annually in the United States, with a heavy concentration in children and adolescents. While early detection offers survival rates up to 75%, those numbers plummet to as low as 5% once the disease metastasizes. By identifying the RNA binding function of closed ezrin, scientists have found t...