ArticleCell death & disease2024
Sprouty genes regulate activated fibroblasts in mammary epithelial development and breast cancer.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 2 citations in OpenAlex.
- The Metabolic-Immune Axis: Amino Acids and Immune Cell Dynamics in Mammary Gland Development and Remodeling.International journal of biological sciences · 2026Review
- Contractile fibroblasts form a transient niche for the branching mammary epithelium.Nature communications · 2025Article
- The Lysine at Position 177 Is Essential to Limit the Inhibitory Capacities of Sprouty4 Protein in Normal and Cancer-Derived Cells.International journal of molecular sciences · 2025Article
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Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
Abstract
Stromal fibroblasts are a major stem cell niche component essential for organ formation and cancer development. Fibroblast heterogeneity, as revealed by recent advances in single-cell techniques, has raised important questions about the origin, differentiation, and function of fibroblast subtypes. In this study, we show in mammary stromal fibroblasts that loss of the receptor tyrosine kinase (RTK) negative feedback regulators encoded by Spry1, Spry2, and Spry4 causes upregulation of signaling in multiple RTK pathways and increased extracellular matrix remodeling, resulting in accelerated epithelial branching. Single-cell transcriptomic analysis demonstrated that increased production of FGF10 due to Sprouty (Spry) loss results from expansion of a functionally distinct subgroup of fibroblasts with the most potent branching-promoting ability. Compared to their three independent lineage precursors, fibroblasts in this subgroup are "activated," as they are located immediately adjacent to the epithelium that is actively undergoing branching and invasion. Spry genes are downregulated, and activated fibroblasts are expanded, in all three of the major human breast cancer subtypes. Together, our data highlight the regulation of a functional subtype of mammary fibroblasts by Spry genes and their essential role in epithelial morphogenesis and cancer development.
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Registered trials
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