ArticleCell communication and signaling : CCS2019
GREM1 is associated with metastasis and predicts poor prognosis in ER-negative breast cancer patients.
Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 56 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
- C/EBP alpha agonist ICCB280 overcomes doxorubicin resistance in osteosarcoma through mitochondrial dynamics-dependent GREM1-MAPK activation.Cell death & disease · 2026Article
- Profibrogenic Gremlin-1 expression in prostate cancer and the clinicopathologic association.Frontiers in oncology · 2026Article
- Dihydrotestosterone and 17β-estradiol modulate TMJ osteoarthritis development and reveal sex-specific differences in pathogenesis.Scientific reports · 2025Article
- The Role of GREMLIN1, a Bone Morphogenetic Protein Antagonist, in Cancer Stem Cell Regulation.Cells · 2025Review
- A comprehensive prognostic and immunological implications of Gremlin 1 in lung adenocarcinoma.Frontiers in immunology · 2025Article
- Gremlin1: a BMP antagonist with therapeutic potential in Oncology.Investigational new drugs · 2024Review
- GREM1 may be a biological indicator and potential target of bladder cancer.Scientific reports · 2024Article
- HLA-G neo-expression modifies genetic programs governing tumor cell lines.Cancer immunology, immunotherapy : CII · 2024Article
- iIMPACT: integrating image and molecular profiles for spatial transcriptomics analysis.Genome biology · 2024Article
- Circular RNA circ_001621 acts as a tumor promoter in lung cancer by regulating the miR-199a-3p/GREM1 axis.Archives of medical science : AMS · 2024Article
- GREM1 signaling in cancer: tumor promotor and suppressor?Journal of cell communication and signaling · 2023Article
- Discovery of a new marker to identify myeloid cells associated with metastatic breast tumours.Cancer cell international · 2023Article
- Opposite and dynamic regulation of the interferon response in metastatic and non-metastatic breast cancer.Cell communication and signaling : CCS · 2023Article
- Profiling and targeting cancer stem cell signaling pathways for cancer therapeutics.Frontiers in cell and developmental biology · 2023Review
- Aberrant expression of bone morphogenetic proteins in the disease progression and metastasis of breast cancer.Frontiers in oncology · 2023Article
- Ten Years of CRISPRing Cancers In Vitro.Cancers · 2022Review
- The emerging era of personalized medicine in advanced colorectal cancer.Journal of gastroenterology and hepatology · 2022Review
- Reciprocal SOX2 regulation by SMAD1-SMAD3 is critical for anoikis resistance and metastasis in cancer.Cell reports · 2022Article
- Gremlin-1 Promotes Colorectal Cancer Cell Metastasis by Activating ATF6 and Inhibiting ATF4 Pathways.Cells · 2022Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn breast cancer, activation of bone morphogenetic protein (BMP) signaling and elevated levels of BMP-antagonists have been linked to tumor progression and metastasis. However, the simultaneous upregulation of BMPs and their antagonist, and the fact that both promote tumor aggressiveness seems contradictory and is not fully understood.
methodsWe analyzed the transcriptomes of the metastatic 66cl4 and the non-metastatic 67NR cell lines of the 4T1 mouse mammary tumor model to search for factors that promote metastasis. CRISPR/Cas9 gene editing was used for mechanistic studies in the same cell lines. Furthermore, we analyzed gene expression patterns in human breast cancer biopsies obtained from public datasets to evaluate co-expression and possible relations to clinical outcome.
resultsWe found that mRNA levels of the BMP-antagonist Grem1, encoding gremlin1, and the ligand Bmp4 were both significantly upregulated in cells and primary tumors of 66cl4 compared to 67NR. Depletion of gremlin1 in 66cl4 could impair metastasis to the lungs in this model. Furthermore, we found that expression of Grem1 correlated with upregulation of several stem cell markers in 66cl4 cells compared to 67NR cells. Both in the mouse model and in patients, expression of GREM1 associated with extracellular matrix organization, and formation, biosynthesis and modification of collagen. Importantly, high expression of GREM1 predicted poor prognosis in estrogen receptor negative breast cancer patients. Analyses of large patient cohorts revealed that amplification of genes encoding BMP-antagonists and elevation of the corresponding transcripts is evident in biopsies from more than half of the patients and much more frequent for the secreted BMP-antagonists than the intracellular inhibitors of SMAD signaling.
conclusionIn conclusion, our results show that GREM1 is associated with metastasis and predicts poor prognosis in ER-negative breast cancer patients. Gremlin1 could represent a novel target for therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.