What if childhood cancer depends on a communication system researchers could learn to interrupt?
At the Greehey Children’s Cancer Research Institute, the Shiio Lab, led by Yuzuru Shiio, studies the molecular signals that help childhood cancers grow and survive. The team combines proteomics—the large-scale study of proteins—with molecular and cellular biology to identify previously unknown relationships between signaling molecules and the receptors that receive their messages.
A major focus of the lab is Ewing sarcoma, an aggressive bone and soft-tissue cancer that primarily affects children, teenagers and young adults.
Cancer cells rely on complicated networks of molecular signals. Think of them as conversations telling a cell when to grow, move or survive. If researchers can determine which conversations a tumor depends on, they may also find ways to shut them down.
That is exactly what the Shiio Lab is working to uncover.
One discovery involves a protein called IGSF10 and a receptor called RET. The lab found that Ewing sarcoma cells depend on IGSF10 and uncovered how it controls RET signaling and another molecule, CDC42, which plays an important role in Ewing sarcoma growth and cell movement. The work, published in Cell Reports in 2025, revealed a previously unrecognized signaling pathway involved in the disease.
The lab has uncovered another potential vulnerability involving ceramide, a lipid molecule that can act as a cellular signal.
Shiio Lab researchers discovered that Ewing sarcoma depends on an enzyme called SMPD1, which generates ceramide, and identified GPR64 as a receptor through which ceramide can trigger signaling important to tumor growth. Importantly, EWS::FLI1, the abnormal fusion protein that drives Ewing sarcoma, controls both SMPD1 and GPR64.
That creates an intriguing possibility.
Instead of attacking EWS::FLI1 directly—one of the notoriously difficult challenges in Ewing sarcoma research—scientists may be able to target some of the molecular dependencies it creates.
These discoveries are still research findings, not established treatments. But identifying pathways that Ewing sarcoma cells rely on gives researchers new places to look for therapeutic vulnerabilities.
Every cancer has biology it depends on. Finding those dependencies can reveal where to attack.
By decoding the molecular conversations that keep Ewing sarcoma growing, the Shiio Lab is helping uncover new strategies that could ultimately lead to more precise and effective treatments for children facing this aggressive cancer.
🔬 Learn more about the Shiio Lab
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