UC San Diego researchers say a shape-shifting protein inside breast cancer cells might be quietly holding back early spread until doctors shut it off. In a new study, the protein TYK2 behaved like a brake pedal on tumor invasion by responding to how stiff or soft the surrounding tissue is. When scientists blocked TYK2 in laboratory models, tumors turned more aggressive and invasive. The work, which ran across engineered tissues, patient-derived organoids and mouse models, suggests that the physical feel of tissue, not just its genetics, can steer how cancers spread. It also lands in a tricky clinical spot, because drugs that shut down TYK2 are already approved or in trials for autoimmune diseases.
UCSD authors urge clinical caution
According to UC San Diego, lead author Zhimin Hu said, "This study reveals how extracellular matrix stiffness regulates breast cancer metastasis." Corresponding author Jing Yang warned that the work "has significant implications for the clinical use of TYK2 inhibitors" and urged that the mechanical tumor microenvironment be considered in therapy decisions. The university release frames the finding as both a mechanistic advance and a cautionary flag for patients on TYK2-blocking drugs.
How stiffness flips TYK2’s role
In a paper published in Nature Communications, the team found that when the extracellular matrix is soft TYK2 localizes at the plasma membrane through association with IFNAR1 and suppresses epithelial-to-mesenchymal transition. When the matrix is stiff TYK2 becomes cytoplasmic and inactive, which allows cells to invade. The authors showed that genetic knockdown or pharmacologic blockade of TYK2 prompted invasion in mammary acini and organoids, and that TYK2 inhibition increased metastasis in xenograft models. The paper pairs molecular imaging with functional tests to show how a protein’s location inside a cell can change tumor behavior.
What this means for patients on TYK2 drugs
Drugs that block TYK2 are already in clinical use and in trials for autoimmune conditions, and product documents from the FDA show SOTYKTU (deucravacitinib) is a marketed TYK2 inhibitor for plaque psoriasis. As reported by The San Diego Union‑Tribune, the paper's mouse tests found that TYK2 inhibitors promoted breast-cancer invasion and metastasis, prompting the authors to recommend enhanced screening for patients receiving these therapies. Researchers stress that the findings are preclinical and do not yet dictate changes to prescribed treatment without further study.
Next steps and takeaways
The authors call for follow-up studies to understand whether tissue mechanics alter risk in people and whether additional breast screening is warranted for patients on TYK2 inhibitors, per UC San Diego. The Nature Communications paper lists funding from the National Cancer Institute and the American Association for Cancer Research, among others. For clinicians and patients, the immediate message is measured vigilance: weigh the clear benefits of TYK2 therapy for autoimmune disease against an emerging preclinical signal that merits targeted clinical follow-up.
