Reposted from U of U Health.
Huntsman Cancer Institute researchers have uncovered a previously unrecognized molecular mechanism by which cells send signals to one another-insight that could help researchers better understand how cancers form and, over time, inform new treatment strategies.
In a study published in Nature Structural & Molecular Biology, the team focuses on the Hedgehog signaling pathway, an essential communication system in human development that is frequently disrupted in cancer.
"Cell signaling is like a conversation happening constantly inside our bodies," said senior author Benjamin Myers, an associate professor of oncological sciences at the University of Utah. "We uncovered a new way that this pathway transmits signals at the molecular level-and that opens the door to new ways of thinking about how these messages go wrong in disease."
A new look at a key cancer pathway
The Hedgehog pathway helps direct how cells grow and specialize during early development. In most adult tissues, it stays largely quiet. But when it switches on at the wrong time or in the wrong place, it can drive cancers such as basal cell carcinoma, the most common cancer in North America, and medulloblastoma, the most common pediatric brain tumor.
For years, scientists thought Hedgehog relied on a single, well-mapped signaling script. Myers and his team show that signal transmission involves a distinct molecular mechanism in which key pathway components interact in a way that differs from traditional textbook models.
Using structural biology approaches, the researchers visualized how key Hedgehog molecules assemble and relay information inside the cell, revealing interactions that were previously difficult to detect.
"This kind of structural insight helps us understand not just that signaling occurs, but how it works," Myers said. "That's essential for designing smarter, more precise therapies in the future."
Why this discovery matters
Understanding cancer-related signaling at a fundamental level is a key step toward better treatments. Drugs that target the Hedgehog pathway already exist, but resistance and side effects limit how well they work.
"This discovery sharpens our view of one of the body's most important signaling systems," said Alana Welm, HCI's senior director of basic science and chair of the U School of Medicine's Department of Oncological Sciences. "With a clearer molecular picture, researchers can start to spot new therapeutic opportunities-approaches that are more precise and may ultimately be more effective for patients."
As the National Cancer Institute-designated Comprehensive Cancer Center for the Mountain West, Huntsman Cancer Institute brings together scientists and clinicians to turn fundamental discoveries into progress against cancer. These latest findings reflect HCI's commitment to combining basic science with clinical impact to improve cancer prevention, diagnosis and treatment.
"By answering fundamental questions about how cells work, we're laying the groundwork for future breakthroughs that can ultimately benefit patients," Welm said.
The study appeared April 30 in the journal under the title, "Structural mechanism for noncanonical GPCR signaling in the Hedgehog pathway." Co-authors from Huntsman Cancer Institute include Will Steiner, Nathan Iverson, Guibing Liu and Zachary Michaelson, as well as scientists from the School of Medicine's Department of Biochemistry. Co-authors from other institutions include Varun Venkatakrishnan, Penn State University; Jian Wu and Susan Taylor, University of California, San Diego; Roland Dunbrack, Fox Chase Cancer Center; and Tomek Stepniewski, Universitat Pompeu Fabra, Barcelona. Funding came from the National Cancer Institute and Huntsman Cancer Foundation.
