New Mechanism Uncovered in Aggressive Breast Cancer Progression: Jagged1 Protein Directs Tumor Remodeling
A research group at Åbo Akademi University, Finland, has identified a previously unknown mechanism involving the protein Jagged1 that directs the remodeling of tumor tissue during the progression of aggressive breast cancer. This discovery, made in collaboration with the University of Turku, may offer new treatment avenues for aggressive forms of breast cancer that currently lack targeted therapies. The findings were published in "Science Advances" on March 18, 2026.
This discovery, made in collaboration with the University of Turku, may offer new treatment avenues for aggressive forms of breast cancer that currently lack targeted therapies.
Understanding Breast Cancer Progression
Breast cancer is globally recognized as the most common cancer among women. While localized, early-stage breast cancer typically carries a favorable prognosis, patient survival rates tend to decrease significantly once the cancer metastasizes to distant organs. Factors such as the breast cancer subtype and the hormone receptor status of cancer cells are known to influence patient survival. Additionally, the communication between cancer cells and other cells within the tumor, alongside their collective ability to shape the surrounding tissue, is increasingly understood as critical for regulating cancer metastasis and drug resistance.
Previous studies had indicated that Jagged1, a protein involved in cell-cell communication, is highly expressed in aggressive, hormone receptor-negative breast cancer. However, its specific functions and precise role in breast cancer progression remained undefined prior to this research.
Jagged1's Critical Role in Tumor Remodeling Unveiled
The new study utilized various cancer model systems and breast cancer patient data to investigate Jagged1. Researchers found that Jagged1 increases breast tumor growth and metastasis and is associated with a less favorable survival prognosis in patients with aggressive breast cancer.
A key finding was the identification of a previously unknown cell communication mechanism between breast cancer cells and fibroblasts, mediated by Jagged1.
Fibroblasts are a type of cell responsible for producing and controlling the extracellular matrix (ECM), a structural network that provides support and signaling cues for cells within tissues. When cancer cells expressed Jagged1 on their surface, it was observed to activate nearby fibroblasts, leading them to produce more ECM components, such as collagen. These Jagged1-activated fibroblasts also modified the structure of the surrounding ECM, creating aligned fibers that can facilitate cancer cell movement during metastasis.
Unpacking the Mechanism: Jagged1 and the TGFβ Pathway
The research further explored how Jagged1 regulates tumor tissue remodeling, revealing that high Jagged1 expression activates the transforming growth factor beta (TGFβ) pathway. TGFβ is a signaling system known to promote tumor progression in late-stage breast cancer and acts as a key regulator of ECM remodeling, contributing to fibrosis, increased tumor stiffness, and metastasis.
The study showed that elevated Jagged1 levels promoted TGFβ activity, which subsequently increased collagen deposition and matrix linearization. Furthermore, the researchers observed that cancer cells expressed higher levels of Jagged1 in stiffer matrix environments.
Previous research has also indicated that TGFβ can drive Jagged1 expression, suggesting a self-promoting cycle that continuously contributes to tumor progression.
Collaborative Effort and Support
This research was conducted by Professor Cecilia Sahlgren's group at Åbo Akademi University and the InFLAMES Research Flagship, in collaboration with Professor Jyrki Heino's research group at the University of Turku, both in Finland.
The study received funding from multiple organizations, including:
- The Research Council of Finland
- Cancer Foundation Finland
- The Finnish Cultural Foundation
- The Swedish Cultural Foundation in Finland
- The Sigrid Jusélius Foundation
- The Jane and Aatos Erkko Foundation
- The Ida Montin Foundation
- The K. Albin Johansson Foundation