Genetic Circuit Found To Drive Glioblastoma Spread
Researchers have pinpointed a gene circuit that propels cancer cell movement in glioblastoma.
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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.(Link is external)
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.
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.
Reference: Shah SR, Ren C, Tippens ND, et al. YAP controls cell migration and invasion through a Rho GTPase switch. Science Signaling. 2025;18(888):eadu3794. doi:10.1126/scisignal.adu3794
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