ArticlePloS one2012
Loss of secreted frizzled-related protein 4 correlates with an aggressive phenotype and predicts poor outcome in ovarian cancer patients.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 59 citations in OpenAlex.
- Article
- Secreted frizzled-related protein 4 (sFRP4) in cancer - Dual roles in tumorigenesis and therapeutic potential: A review.Biomolecules & biomedicine · 2025Review
- PKA-Mediated Phosphorylation of SFRP4 Promotes Wnt/β-Catenin Activation and Cancer Stemness in Gastric Cancer.International journal of molecular sciences · 2025Article
- New treatment strategies for uterine sarcoma using secreted frizzled‑related proteins.Experimental and therapeutic medicine · 2024Article
- Review
- Interactome of Paraoxonase PON2 Reveals New Pathways for Tumor Growth Regulation.Doklady. Biochemistry and biophysics · 2023Article
- Diagnostic and prognostic role of TFF3, Romo-1, NF-кB and SFRP4 as biomarkers for endometrial and ovarian cancers: a prospective observational translational study.Archives of gynecology and obstetrics · 2022Observational
- Wnt antagonist as therapeutic targets in ovarian cancer.The international journal of biochemistry & cell biology · 2022Review
- SFRP4 Is a Potential Biomarker for the Prognosis and Immunotherapy for Gastric Cancer.Journal of oncology · 2022Article
- KDF1 Promoted Proliferation and Metastasis of Epithelial Ovarian CancerFrontiers in genetics · 2022Article
- TRIB2 Stimulates Cancer Stem-Like Properties through Activating the AKT-GSK3β-β-Catenin Signaling Axis.Molecules and cells · 2021Article
- The miR-181a-SFRP4 Axis Regulates Wnt Activation to Drive Stemness and Platinum Resistance in Ovarian Cancer.Cancer research · 2021Article
- Secreted Frizzled-Related Protein 4 (SFRP4) Is an Independent Prognostic Marker in Prostate Cancers Lacking TMPRSS2: ERG Fusions.Pathology oncology research : POR · 2020Article
- Wnt/β-catenin signalling in ovarian cancer: Insights into its hyperactivation and function in tumorigenesis.Journal of ovarian research · 2019Review
- Outcome in serous ovarian cancer is not associated with LATS expression.Journal of cancer research and clinical oncology · 2019Article
- Wnt Signaling in Ovarian Cancer Stemness, EMT, and Therapy Resistance.Journal of clinical medicine · 2019Review
- A phase 1b dose escalation study of ipafricept (OMP54F28) in combination with paclitaxel and carboplatin in patients with recurrent platinum-sensitive ovarian cancer.Gynecologic oncology · 2019Article
- Stemness, Pluripotentiality, and Wnt Antagonism: sFRP4, a Wnt antagonist Mediates Pluripotency and Stemness in Glioblastoma.Cancers · 2018Article
- Potential signaling pathways as therapeutic targets for overcoming chemoresistance in mucinous ovarian cancer.Biomedical reports · 2018Article
- Human epicardial adipose tissue-derived and circulating secreted frizzled-related protein 4 (SFRP4) levels are increased in patients with coronary artery disease.Cardiovascular diabetology · 2017Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundActivation of the Wnt signaling pathway is implicated in aberrant cellular proliferation in various cancers. In 40% of endometrioid ovarian cancers, constitutive activation of the pathway is due to oncogenic mutations in β-catenin or other inactivating mutations in key negative regulators. Secreted frizzled-related protein 4 (SFRP4) has been proposed to have inhibitory activity through binding and sequestering Wnt ligands. METHODOLOGY/PRINCIPAL
findingsWe performed RT-qPCR and Western-blotting in primary cultures and ovarian cell lines for SFRP4 and its key downstream regulators activated β-catenin, β-catenin and GSK3β. SFRP4 was then examined by immunohistochemistry in a cohort of 721 patients and due to its proposed secretory function, in plasma, presenting the first ELISA for SFRP4. SFRP4 was most highly expressed in tubal epithelium and decreased with malignant transformation, both on RNA and on protein level, where it was even more profound in the membrane fraction (p<0.0001). SFRP4 was expressed on the protein level in all histotypes of ovarian cancer but was decreased from borderline tumors to cancers and with loss of cellular differentiation. Loss of membrane expression was an independent predictor of poor survival in ovarian cancer patients (p = 0.02 unadjusted; p = 0.089 adjusted), which increased the risk of a patient to die from this disease by the factor 1.8. CONCLUSIONS/SIGNIFICANCE: Our results support a role for SFRP4 as a tumor suppressor gene in ovarian cancers via inhibition of the Wnt signaling pathway. This has not only predictive implications but could also facilitate a therapeutic role using epigenetic targets.
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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 OpenQuestion graph.