Rotating magnetic field downregulating type XI collagen to suppress triple-negative breast cancer metastasis by inactivating the ITGB1/FAK/YAP signaling pathway

Triple-negative breast cancer (TNBC) exhibits a strong tendency for both metastasis and recurrence. Therefore, identifying new targeted therapies or treatment strategies is crucial for improving TNBC outcomes. The extracellular matrix (ECM), which exhibits prominent mechanical sensitivity, is the first barrier that must be crossed during metastasis. Based on our analysis, collagen type XI (COL11A1), a key collagen in the ECM, ranks second among all aberrantly expressed collagens in TNBC. Rotating magnetic fields (RMFs) have garnered significant attention in tumor treatment. However, their specific biological roles and mechanisms involved still need to be further explored. We discovered that COL11A1 promoted TNBC metastasis by binding to the integrin β1 (ITGB1), and this activation initiated the FAK/YAP cascade, driving the malignant behavior of TNBC cells. Notably, COL11A1 was reduced following exposure to RMF. To explore the in vivo impact, COL11A1 siRNA was encapsulated within exosomes (EXOs) for stable delivery. It revealed that both COL11A1 siRNA and RMF effectively suppressed tumor growth and lung metastasis, an effect reversed by ITGB1 agonist. Moreover, the therapeutic effect was further enhanced by combining RMF and COL11A1 siRNA. These findings suggested COL11A1 as a potential TNBC therapeutic target, with COL11A1 siRNA combined with RMF offering a viable treatment strategy.