Summary
Published in Science Advances (2026), this peer-reviewed study used 3D Petri Dish® micro-molds to form scaffold-free 3D microtissues. Full citation: Parikainen, Marjaana, et al. Jagged1 regulates extracellular matrix deposition and remodeling in triple-negative breast cancer
Jagged1 regulates extracellular matrix deposition and remodeling in triple-negative breast cancer
Research Overview
Extracellular-matrix heterogeneity in the tumor microenvironment drives cancer progression and treatment resistance. In triple-negative breast cancer, high Jagged1 expression tracks with poor survival and promotes growth and invasion. Using transcriptomics, proteomics, and imaging of cancer-cell/fibroblast co-cultures both in vitro and in vivo, this study showed that Jagged1-mediated cross-talk between tumor cells and fibroblasts enhances myofibroblast activation, collagen accumulation, and alignment of matrix fibers.
In single-cell RNA sequencing of TNBC tumors, high Jagged1 gives rise to a myofibroblast subpopulation previously linked to enhanced invasion. Jagged1 raised TGFβ activity in fibroblast co-cultures, and blocking TGFβ prevented the Jagged1-induced matrix alignment — placing Jagged1 upstream of TGFβ in reshaping the tumor stroma.
Key Discoveries
- Jagged1 signaling from TNBC cells to fibroblasts increased myofibroblast activation, collagen deposition, and fiber alignment
- High Jagged1 tumors harbor an invasion-associated myofibroblast subpopulation in single-cell RNA-seq
- TGFβ inhibition blocked Jagged1-induced ECM alignment, placing TGFβ downstream of Jagged1
