A study by researchers at the University of California, San Diego may make it easier to treat breast cancer by uncovering a new way the body prevents it from spreading. Researchers have discovered a new role for an inflammatory protein called TYK2 in mechanotransduction, the process by which cells sense and respond to their physical environment. Understanding mechanical transmission provides insight into how cancer spreads and provides new therapeutic avenues.
Furthermore, as drugs that inhibit TYK2 are being investigated as treatments for autoimmune diseases, this study highlights the need to consider the effects of these drugs on breast cancer progression.
The researchers discovered that:
- TYK2 functions as an important breast cancer metastasis suppressor in response to the stiffness of the extracellular matrix, the material that surrounds and binds cells.
- When stiffness is low, TYK2 resides on the cell membrane and blocks cancer cell invasion. When stiff, TYK2 is inactivated and present throughout the cell, allowing cancer cell invasion.
- In mice, inhibiting TYK2 with drugs promoted breast cancer invasion and metastasis.
Understanding how TYK2 functions as a metastasis suppressor could pave the way for new treatments for breast cancer. The findings also suggest that patients with certain types of non-invasive breast cancer may be at increased risk of developing invasive breast cancer if they receive TYK2 inhibitors. This highlights the need for increased breast cancer screening in patients treated with TYK2 inhibitors.
This study reveals how extracellular matrix stiffness regulates breast cancer metastasis through TYK2 and provides new insights into how physical cues in the tumor microenvironment control cancer progression. ”
Dr. Zhimin Hu, lead author of this study and project scientist at UC San Diego Moores Cancer Center
“Our findings have important implications for the clinical use of TYK2 inhibitors and highlight the importance of considering the mechanical microenvironment in cancer treatment,” said corresponding author Jing Yang, Ph.D., professor of pharmacology at the University of California, San Diego School of Medicine. Mr. Yang is also a member of the Moores Cancer Center.
sauce:
University of California, San Diego
Reference magazines:
Hu, Z. Others. (2026). Extracellular matrix stiffness controls breast cancer metastasis via TYK2-mediated mechanotransduction. Nature Communications. DOI: 10.1038/s41467-026-70518-9. https://www.nature.com/articles/s41467-026-70518-9
