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Ref Type Journal Article
PMID (30096373)
Authors Xie W, Zhang Y, He Y, Zhang K, Wan G, Huang Y, Zhou Z, Huang G, Wang J
Title A novel recombinant human Frizzled-7 protein exhibits anti-tumor activity against triple negative breast cancer via abating Wnt/β-catenin pathway.
Journal The international journal of biochemistry & cell biology
Vol 103
Issue
Date 2018 10
URL
Abstract Text Triple negative breast cancer (TNBC) is one of the most difficult malignancy to treat due to a lack of targeted therapy. Studies have demonstrated that the activation of Wnt/β-catenin signaling was preferentially found in TNBC. Frizzled-7 (Fzd7), one of the Wnt receptors, was significantly up-regulated in TNBC and modulated TNBC tumorigenesis through the Wnt signaling pathway, indicating Fzd7 is a biomarker and a potential therapeutic target for TNBC. Here, we designed a recombinant soluble peptide fragment (rhFzd7) to antagonize Fzd7 by competitively binding with Wnt ligands. We demonstrated the ability of rhFzd7 to bind to its ligand, Wnt3a, and monitored the kinetic process using a Biacore X100 system. In addition, the anti-tumor and anti-angiogenic activity of rhFzd7 were studied in vitro and in vivo. Results showed that the purified rhFzd7 pulled down Wnt3a from MDA-MB-231 cells and exhibited high affinity with Wnt3a (KD: 3.41 × 10-8 M). The data in vitro revealed that rhFzd7 inhibited proliferation and invasion of TNBC cells, and induced apoptosis of TNBC cells effectively. The anti-angiogenic assay indicated that rhFzd7 repressed TNBC angiogenesis in vitro and in vivo. Furthermore, the study in vivo showed that rhFzd7 could sensitize TNBC cells to the anti-tumor effect of Docetaxel. In conclusion, the generation of rhFzd7 lays foundation for the screening of anti-Fzd7 antibody, and this novel design provides an effective candidate for the clinical treatment of TNBC.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
RhFzd7 WNT Inhibitor 10 RhFzd7 is peptide fragment that consists of the extracellular domain of Frizzled 7 (Fzd7), which binds to Wnt3a and competes with binding to Fzd7, potentially resulting in apoptosis and inhibition of cellular invasion and proliferation (PMID: 30096373).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown triple-receptor negative breast cancer not applicable Docetaxel + RhFzd7 Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with the combination of RhFzd7 and Taxotere (docetaxel) resulted in increased inhibition of proliferation and decreased tumor growth and neovascularization compared to either agent alone in cell line xenograft models of triple-negative breast cancer (PMID: 30096373). 30096373
Unknown unknown triple-receptor negative breast cancer not applicable RhFzd7 Preclinical - Cell line xenograft Actionable In a preclinical study, RhFzd7 treatment inhibited cellular proliferation, invasion, and induced apoptosis in triple-negative breast cancer cell lines in culture, and inhibited tumor growth in cell line xenograft models (PMID: 30096373). 30096373