ArticleNature cancer2022
Gremlin1 is a therapeutically targetable FGFR1 ligand that regulates lineage plasticity and castration resistance in prostate cancer.
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Article in Nature cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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42citing papers in PubMed, 1 pooled it
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42 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Identification of novel protein biomarkers and drug targets for colorectal cancer by integrating human plasma proteome with genome.Genome medicine · 2023Pooled it
- Gremlin-1 Drives Tumour Vascularization by Promoting Endothelial Differentiation and Angiogenesis.Journal of cellular and molecular medicine · 2026Article
- A paracrine-to-autocrine shunt of GREM1 fuels colorectal cancer metastasis via ACVR1C.Molecular cancer · 2026Article
- Inhibition of LONP1 in prostate cancer: bibliometrics-guided target screening and AI-driven antibody design.International journal of surgery (London, England) · 2026Article
- Fibroblast-derived gremlin-1 Is associated with ovarian cancer-cell phenotypes in co-culture models.Frontiers in oncology · 2026Article
- Immune-tumor cell ligand-receptor axes driving metabolic reprogramming and therapeutic resistance in cancer.Frontiers in immunology · 2026Review
- Profibrogenic Gremlin-1 expression in prostate cancer and the clinicopathologic association.Frontiers in oncology · 2026Article
- FAM111B promotes prostate cancer progression by inhibiting apoptosis via ATF3 suppression and MAPK pathway activation: a novel biomarker and therapeutic target.Cancer cell international · 2025Article
- Periodic asymmetric field enhances electrofusion of nanoscale lipid systems.Nature communications · 2025Article
- Molecular profiling of ex vivo prostate cancer CAF models captures stromal heterogeneity and drug vulnerabilities.Cell death discovery · 2025Article
- Hepatocyte-Specific GSDMD Deficiency Aggravates Sepsis by Disrupting Non-Canonical Secretion of Anti-Inflammatory Factors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Discovery and Characterization of Novel FGFR1 V561M Inhibitors via Virtual Screening and Molecular Dynamics Simulations.ACS medicinal chemistry letters · 2025Article
- BMP signalling in colorectal cancer: losing the yin to WNTs yang.The Journal of pathology · 2025Review
- [Apelin promotes proliferation, migration, and angiogenesis in bladder cancer by activating the FGF2/FGFR1 pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Epithelial GREMLIN1 disrupts intestinal epithelial-mesenchymal crosstalk to induce a wnt-dependent ectopic stem cell niche through stromal remodelling.Nature communications · 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
- Ex.50.T aptamer impairs tumor-stroma cross-talk in breast cancer by targeting gremlin-1.Cell death discovery · 2025Article
- Sex hormones, blood metabolites and proteins mediating the causal associations between gut microbiota and prostatic diseases: evidences from Mendelian randomization study.Prostate international · 2025Article
- Osteoblast-Derived ECM1 Promotes Anti-Androgen Resistance in Bone Metastatic Prostate Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
28 authors at 4 institutions in 1 country.
Chaping Cheng *State Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Shanghai Cancer Institute & Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jinming Wang *State Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Shanghai Cancer Institute & Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Penghui XuState Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Shanghai Cancer Institute & Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Kai ZhangState Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Shanghai Cancer Institute & Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhixiang XinState Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Shanghai Cancer Institute & Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Huifang ZhaoState Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Shanghai Cancer Institute & Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhongzhong JiState Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Shanghai Cancer Institute & Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Man ZhangSchool of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.ORCID http://orcid.org/0000-0002-0240-0871
Deng WangState Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Shanghai Cancer Institute & Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yuman HeState Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Shanghai Cancer Institute & Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Na JingState Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Shanghai Cancer Institute & Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Liancheng FanState Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Shanghai Cancer Institute & Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Kaiyuan LiuState Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Shanghai Cancer Institute & Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Fei LiState Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.
Chengcheng LiuState Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Shanghai Cancer Institute & Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yiming GongState Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Shanghai Cancer Institute & Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Suli CuiMabspace Biosciences (Suzhou) Co., Ltd, Suzhou, China.
Zhe SunMabspace Biosciences (Suzhou) Co., Ltd, Suzhou, China.
Di SunMabspace Biosciences (Suzhou) Co., Ltd, Suzhou, China.
Xinlai YaoMabspace Biosciences (Suzhou) Co., Ltd, Suzhou, China.
Hongjun LiMabspace Biosciences (Suzhou) Co., Ltd, Suzhou, China.
Jian ZhangKey Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education & School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.ORCID http://orcid.org/0000-0002-6558-791X
Pengcheng ZhangState Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0000-0002-4546-0022
Baijun DongState Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Shanghai Cancer Institute & Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID http://orcid.org/0000-0002-5721-9586
Wei XueState Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Shanghai Cancer Institute & Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xueming QianMabspace Biosciences (Suzhou) Co., Ltd, Suzhou, China.
Wei-Qiang GaoState Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Shanghai Cancer Institute & Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. gao.weiqiang@sjtu.edu.cn.ORCID http://orcid.org/0000-0002-1989-4927
Helen He ZhuState Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Shanghai Cancer Institute & Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. zhuhecrane@shsmu.edu.cn.ORCID http://orcid.org/0000-0003-0290-5527
Shanghai Jiao Tong University · CNBioscience (China) · CNChinese Academy of Sciences · CNZhengzhou University · CN
Funding
No grant is acknowledged in the PubMed record.
Abstract
Among the greatest hurdles in clinical management of prostate cancer (PCa) are the progression to lethal castration-resistant prostate cancer (CRPC) and the lack of suitable targeted therapies for advanced disease. Here we identify Gremlin1 as a ligand for fibroblast growth factor receptor 1 (FGFR1), which promotes lineage plasticity and drives castration resistance. Importantly, we generate a specific anti-Gremlin1 therapeutic antibody and demonstrate synergistic effect with androgen deprivation therapy (ADT) in CRPC. GREM1 transcription is suppressed by androgen receptor (AR) and released following ADT. We show that Gremlin1 binds to FGFR1 and activates downstream MAPK signaling. Gremlin1 interacts with FGFR1 differently to its canonical ligand FGF1, as revealed through protein structure docking and mutagenesis experiments. Altogether, our data indicate Gremlin1 as a promising candidate therapeutic target for CRPC.
Indexed as
Prostatic Neoplasms, Castration-ResistantAndrogen AntagonistsCastrationHumansIntercellular Signaling Peptides and ProteinsLigandsMaleReceptor, Fibroblast Growth Factor, Type 1Signal TransductionAndrogen AntagonistsFGFR1 protein, humanGREM1 protein, humanIntercellular Signaling Peptides and ProteinsLigandsReceptor, Fibroblast Growth Factor, Type 1
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