ArticleBreast cancer research : BCR2019
Cancer-associated fibroblast-derived Gremlin 1 promotes breast cancer progression.
Article in Breast cancer research : BCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 173 citations in OpenAlex.
- A dose-finding population pharmacokinetic/pharmacodynamic model of ginisortamab, an anti-gremlin-1 monoclonal antibody, in patients with solid tumours.British journal of clinical pharmacology · 2026Article
- In vitro multi-organ invasion model for exploring cardiac resistance to cancer metastasis.Nature communications · 2026Article
- Gremlin-1 Drives Tumour Vascularization by Promoting Endothelial Differentiation and Angiogenesis.Journal of cellular and molecular medicine · 2026Article
- Genetic risk factors modulate the association between physical activity and colorectal cancer.BMC medicine · 2026Article
- Surface-Associated Proteins on Extracellular Vesicles Remodel the Tumor Microenvironment by Potentiating TGF-β Signaling in a Contact-Dependent Manner.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A paracrine-to-autocrine shunt of GREM1 fuels colorectal cancer metastasis via ACVR1C.Molecular cancer · 2026Article
- Profibrogenic Gremlin-1 expression in prostate cancer and the clinicopathologic association.Frontiers in oncology · 2026Article
- Novel anti-tumor strategies: targeting the crosstalk between cancer stem cells and cancer-associated fibroblasts to resist drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Collagen dynamics in the breast cancer tumor microenvironment and therapeutic perspectives.Discover oncology · 2025Review
- Bibliometric analysis reveals the current status and future trends of cancer associated fibroblasts research in breast cancer.Discover oncology · 2025Article
- Cancer‑associated fibroblasts in human malignancies, with a particular emphasis on sarcomas (Review).International journal of oncology · 2025Review
- Genetic risk factors modulate the association between physical activity and colorectal cancer.Research square · 2025Article
- Lung cancer intravasation-on-a-chip: Visualization and machine learning-assisted automatic quantification.Bioactive materials · 2025Article
- Identification ofCancers · 2025Article
- CAF-derived exosomes drive the FGF4/SHH feedback loop by encapsulating GREM1 in non-small cell lung cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- A Validated Proteomic Signature of Basal-like Triple-Negative Breast Cancer Subtypes Obtained from Publicly Available Data.Cancers · 2025Article
- GREM1 deficiency induced bone marrow adipose niche promotes B-cell acute lymphoblastic leukemia disease progression.International journal of cancer · 2025Article
- LA-peptide Hydrogel-Regulation of macrophage and fibroblast fates and their crosstalk via attenuating TGF-β to promote scarless wound healing.Bioactive materials · 2025Article
- The Role of GREMLIN1, a Bone Morphogenetic Protein Antagonist, in Cancer Stem Cell Regulation.Cells · 2025Review
- A Gremlin 1-expressing splenic niche cell population restrains chronic myeloid leukemia by antagonizing the BMP pathway.Nature cancer · 2025Article
46 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBone morphogenetic proteins (BMPs) have been reported to maintain epithelial integrity and to antagonize the transforming growth factor β (TGFβ)-induced epithelial to mesenchymal transition. The expression of soluble BMP antagonists is dysregulated in cancers and interrupts proper BMP signaling in breast cancer.
methodsIn this study, we mined the prognostic role of BMP antagonists GREMLIN 1 (GREM1) in primary breast cancer tissues using in-house and publicly available datasets. We determined which cells express GREM1 RNA using in situ hybridization (ISH) on a breast cancer tissue microarray. The effects of Grem1 on the properties of breast cancer cells were assessed by measuring the mesenchymal/stem cell marker expression and functional cell-based assays for stemness and invasion. The role of Grem1 in breast cancer-associated fibroblast (CAF) activation was measured by analyzing the expression of fibroblast markers, phalloidin staining, and collagen contraction assays. The role of Grem1 in CAF-induced breast cancer cell intravasation and extravasation was studied by utilizing xenograft zebrafish breast cancer (co-) injection models.
resultsExpression analysis of clinical breast cancer datasets revealed that high expression of GREM1 in breast cancer stroma is correlated with a poor prognosis regardless of the molecular subtype. The large majority of human breast cancer cell lines did not express GREM1 in vitro, but breast CAFs did express GREM1 both in vitro and in vivo. Transforming growth factor β (TGFβ) secreted by breast cancer cells, and also inflammatory cytokines, stimulated GREM1 expression in CAFs. Grem1 abrogated bone morphogenetic protein (BMP)/SMAD signaling in breast cancer cells and promoted their mesenchymal phenotype, stemness, and invasion. Moreover, Grem1 production by CAFs strongly promoted the fibrogenic activation of CAFs and promoted breast cancer cell intravasation and extravasation in co-injection xenograft zebrafish models.
conclusionsOur results demonstrated that Grem1 is a pivotal factor in the reciprocal interplay between breast cancer cells and CAFs, which promotes cancer cell invasion. Targeting Grem1 could be beneficial in the treatment of breast cancer patients with high Grem1 expression.
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