Read Time: 3 minutes
Takeaways:
- Researchers identified a previously unrecognized molecular mechanism cells can use to pass along signals.
- The finding resolves a longstanding puzzle for how the Hedgehog signaling pathway works—one of the most important but mysterious systems in human development and cancer.
Impact: A clearer map of this signaling may help scientists design more precise therapies and understand why some treatments stop working.
A team at Huntsman Cancer Institute
at the University of Utah (the U) has 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 the study, published in Nature Structural & Molecular Biology, the researchers focus 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,” says Benjamin Myers, PhD, investigator at Huntsman Cancer Institute, associate professor of oncological sciences at the U, and senior author of the study. “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 says. “That’s essential for designing smarter, more precise therapies in the future.”
“Cell signaling is like a conversation happening constantly inside our bodies.”
Benjamin Myers, PhD
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 can limit how well they work.
“This discovery sharpens our view of one of the body’s most important signaling systems,” says Alana Welm, PhD, senior director of basic science at Huntsman Cancer Institute and chair of the Department of Oncological Sciences at the U. “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.”
“With a clearer molecular picture, researchers can start to spot new therapeutic opportunities."
Alana Welm, PhD
Advancing cancer research in the Mountain West and beyond
As the National Cancer Institute-designated Comprehensive Cancer Center for the Mountain West, Huntsman Cancer Institute brings together world-class scientists and clinicians to turn fundamental discoveries into progress against cancer. Discoveries like this reflect the institute’s commitment to combining basic science with clinical impact to improve cancer prevention, diagnosis, and treatment.
“This work highlights decades of federally- and donor-funded research," Welm says. “By answering fundamental questions about how cells work, we’re laying the groundwork for future breakthroughs that can ultimately benefit patients.”
Co-authors of the study from Huntsman Cancer Institute include Will Steiner, research trainee; Nathan Iverson, research technician; Guibing Liu, PhD, postdoctoral research associate; and Zachary Michaelson, investigator. Co-authors from other institutions include Varun Venkatakrishnan, Penn State University; Jian Wu and Susan Taylor, PhD, University of California, San Diego; Roland Dunbrack, PhD, Fox Chase Cancer Center; and Tomek Stepniewski, PhD, Universitat Pompeu Fabra, Barcelona.