ArticleScience advances2026
Jagged1 regulates extracellular matrix deposition and remodeling in triple-negative breast cancer.
Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Fibroblast-associated TPM2 links cell-matrix remodeling to EMT-Notch signaling and gemcitabine resistance in intrahepatic cholangiocarcinoma.Cancer biology & therapy · 2026Article
- Unraveling the roles of fibroblast activation protein‑positive cancer‑associated fibroblasts in cancer: From mechanisms to therapy (Review).International journal of oncology · 2026Review
- Investigating Spectral Biomarker Candidates for Migratory Potential in Cancer Cells Using Micro-FTIR and O‑PTIR Spectroscopy.ACS measurement science au · 2026Article
- Exercise and antitumor immunity: molecular signaling, immune dynamics, and remodeling of the tumor microenvironment.Frontiers in immunology · 2026Review
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The extracellular matrix (ECM) and tumor microenvironment heterogeneity drive cancer progression and treatment resistance. High Jagged1 expression correlates with poor patient survival and promotes tumor growth and invasion in triple-negative breast cancer (TNBC). Using transcriptomics, proteomics, and imaging of cancer cell/fibroblast cocultures in vitro and in vivo, we demonstrate that Jagged1-mediated cross-talk between TNBC cells and fibroblasts enhances myofibroblast activation, collagen accumulation, and alignment of ECM fibers. In single-cell RNA sequencing data of TNBC tumors, high Jagged1 expression gives rise to a myofibroblast subpopulation previously associated with enhanced invasion. Jagged1 increases transforming growth factor-β (TGFβ) activity in fibroblast cocultures, and TGFβ inhibition prevents the Jagged1-induced ECM alignment. Thus, Jagged1 regulates ECM remodeling upstream of TGFβ. Furthermore, higher substrate stiffness up-regulates Jagged1, suggesting a feed-forward loop between Jagged1, ECM stiffness, and TGFβ. With the emergence of safe therapeutics targeting specific Notch components, Jagged1 modulation may offer an approach for treating invasive breast cancer.
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