ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Secreted Frizzled-Related Protein 3 (SFRP3) Is Required for Tumorigenesis of PAX3-FOXO1-Positive Alveolar Rhabdomyosarcoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 21 citations in OpenAlex.
- Fusion-positive rhabdomyosarcoma oncofusions share a common interactome.Nature communications · 2026Article
- Towards directed therapy for fusion-positive rhabdomyosarcoma.Pharmacology & therapeutics · 2025Review
- Article
- Epigenetic regulation of mitochondrial fission and cardiac fibrosis via sFRP3 promoter methylation.Cellular and molecular life sciences : CMLS · 2024Article
- The Wnt-pathway corepressor TLE3 interacts with the histone methyltransferase KMT1A to inhibit differentiation in Rhabdomyosarcoma.Oncogene · 2024Article
- Identification and targeting of a HES1-YAP1-CDKN1C functional interaction in fusion-negative rhabdomyosarcoma.Molecular oncology · 2022Article
- Tumor suppressive functions of WNT5A in rhabdomyosarcoma.International journal of oncology · 2022Article
- Review
- Overexpressed sFRP3 exerts an inhibitory effect on hepatocellular carcinoma via inactivation of the Wnt/β-catenin signaling pathway.Cancer gene therapy · 2021Article
- Molecular mechanisms underpinning sarcomas and implications for current and future therapy.Signal transduction and targeted therapy · 2021Review
- Establishment and characterization of a novel alveolar rhabdomyosarcoma cell line, NCC-aRMS1-C1.Human cell · 2020Article
- KDM3A/Ets1 epigenetic axis contributes to PAX3/FOXO1-driven and independent disease-promoting gene expression in fusion-positive Rhabdomyosarcoma.Molecular oncology · 2020Article
- Frizzled related protein deficiency impairs muscle strength, gait and calpain 3 levels.Orphanet journal of rare diseases · 2020Article
- Genetics, epigenetics and redox homeostasis in rhabdomyosarcoma: Emerging targets and therapeutics.Redox biology · 2019Review
- JARID2 and the PRC2 complex regulate skeletal muscle differentiation through regulation of canonical Wnt signaling.Epigenetics & chromatin · 2018Article
- The Transcriptional Coactivator TAZ Is a Potent Mediator of Alveolar Rhabdomyosarcoma Tumorigenesis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Soft Tissue Sarcoma Cancer Stem Cells: An Overview.Frontiers in oncology · 2018Review
- Advances in sarcoma diagnostics and treatment.Oncotarget · 2017Review
- A Review: Molecular Aberrations within Hippo Signaling in Bone and Soft-Tissue Sarcomas.Frontiers in oncology · 2015Review
- Comprehensive Analysis of the Expression and Prognosis forCell transplantationArticle
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
purposeRhabdomyosarcoma (RMS) is a soft tissue sarcoma associated with the skeletal muscle lineage. Of the two predominant subtypes, known as embryonal (eRMS) and alveolar (aRMS), aRMS has the poorer prognosis, with a five-year survival rate of <50%. The majority of aRMS tumors express the fusion protein PAX3-FOXO1. As PAX3-FOXO1 has proven chemically intractable, this study aims to identify targetable proteins that are downstream from or cooperate with PAX3-FOXO1 to support tumorigenesis. EXPERIMENTAL
designMicroarray analysis of the transcriptomes of human skeletal muscle myoblasts expressing PAX3-FOXO1 revealed alteration of several Wnt pathway gene members, including secreted frizzled related protein 3 (SFRP3), a secreted Wnt pathway inhibitor. Loss-of-function using shRNAs against SFRP3 was used to interrogate the role of SFRP3 in human aRMS cell lines in vitro and conditional murine xenograft systems in vivo. The combination of SFRP3 genetic suppression and the chemotherapeutic agent vincristine was also examined.
resultsIn vitro, suppression of SFRP3 inhibited aRMS cell growth, reduced proliferation accompanied by a G1 arrest and induction of p21, and induced apoptosis. In vivo, doxycycline-inducible suppression of SFRP3 reduced aRMS tumor growth and weight by more than three-fold, in addition to increasing myogenic differentiation and β-catenin signaling. The combination of SFRP3 suppression and vincristine was more effective at reducing aRMS cell growth in vitro than either treatment alone, and ablated tumorigenesis in vivo.
conclusionsSFRP3 is necessary for the growth of human aRMS cells both in vitro and in vivo and is a promising new target for investigation in aRMS.
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