Yale-Mayo Clinic partnership uncovers genetic circuit for brain cancer

Thursday, May 29, 2025
Aggressive cancer cells behave differently

Aggressive cancer cells behave differently, spreading and ultimately damaging the tissues they invade. 

By Jon Atherton

Most of the cells in our bodies don’t move – they stay where they’re supposed to in service to our organs and biological systems. But aggressive cancer cells behave differently, spreading and ultimately damaging the tissues they invade. 

What drives cell invasion has remained a key question for scientists trying to decipher the molecular circuitry responsible for the spread, and high mortality rates, of the most aggressive cancers.

Scholars at the Yale Systems Biology Institute and the Mayo Clinic have now identified clues about how these cells get moving, an important step towards fine tuning cancer prognosis and potential new treatments for the deadly brain cancer, glioblastoma. 

Their findings were published in the current issue of Science Signaling.

Glioblastoma is an incurable cancer with an average survival time after diagnosis of around 12-18 months, with only around 5% of patients surviving five years, according to the Glioblastoma Foundation. 

Bridging the science labs of Andre Levchenko, the John C. Malone Professor of Biomedical Engineering and Director of the Yale Systems Biology Institute, and Alfredo Quinones-Hinojosa, William J. and Charles H. Mayo Professor and Chair of Neurologic Surgery at the Mayo Clinic, Florida, the collaborators were able to conduct experiments with cells extracted from patient tumors to explore the molecular circuits guiding their behaviors.

This research was done in partnership with the National Institutes of Health (NIH) through a grant that includes reimbursement for facilities and administrative expenses (also known as indirect cost reimbursements) that are necessary to ensure the safe conduct of research and compliance with federal regulations.

In February, the NIH announced it would dramatically cut such reimbursements to universities, including Yale. The courts have temporarily blocked the cuts, but the threat remains. 

At stake is research that saves lives, strengthens the economy, and bolsters national interests. Yale projects in danger include research that saves infants born with heart defects, extends the lives of cancer patients, addresses mental health challenges, and prevents and slows the effects of Alzheimer’s disease. 

The study identified a previously missing link between an active mechanical sensor molecule in brain tumors, called YAP, which the scientists observed activating ‘TRIO’ protein to propel cell movement. 

With the new data, the Yale and Mayo labs have developed a gene-based ‘prognostic signature’ that they hope will provide crucial information to help patients and their physicians to better predict survival rates. The researchers are also exploring TRIO as a target for new therapies to slow glioblastoma progression and improve quality of life and patient survival.  

The research was led by Sagar Shah and Chunxiao Ren, former and current members of the Levchenko and Hinojosa’s labs. 

This research was funded by the National Institutes of Health.