ArticleProceedings of the National Academy of Sciences of the United States of America2019
Down-regulation of FZD3 receptor suppresses growth and metastasis of human melanoma independently of canonical WNT signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 63 citations in OpenAlex.
- The Wnt receptor Frizzled3 (FZD3) drives aggressive phenotypes in small cell lung cancer.Respiratory research · 2026Article
- WNT signaling in cancer: molecular mechanisms and potential therapies.Molecular biomedicine · 2025Review
- Cancer Stem Cells in Melanoma: Drivers of Tumor Plasticity and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Treatment of advanced‑stage non‑small cell lung cancer: Current progress and a glimpse into the future (Review).Molecular and clinical oncology · 2025Review
- SOX21-AS1 Augmented Cervical Cancer Growth by Triggering FZD3 to Activate the Wnt/β-Catenin Signaling Pathway.Biochemical genetics · 2025Article
- Comprehensive single-cell atlas of colorectal neuroendocrine tumors with liver metastases: unraveling tumor microenvironment heterogeneity between primary lesions and metastases.Molecular cancer · 2025Article
- Frizzled receptors: gatekeepers of Wnt signaling in development and disease.Frontiers in cell and developmental biology · 2025Review
- The biological role and molecular mechanism of transfer RNA-derived small RNAs in tumor metastasis.Frontiers in oncology · 2025Review
- CircTEC Inhibits the Follicular Atresia in Buffalo (International journal of molecular sciences · 2024Article
- CTHRC1 is associated withBiomolecules & biomedicine · 2024Article
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- Structural insights into Frizzled3 through nanobody modulators.Nature communications · 2024Article
- Frizzled receptors (FZDs) in Wnt signaling: potential therapeutic targets for human cancers.Acta pharmacologica Sinica · 2024Review
- The roles of cancer stem cells and therapeutic implications in melanoma.Frontiers in immunology · 2024Review
- NRF-1 transcription factor regulates expression of an innate immunity checkpoint, CD47, during melanomagenesis.Frontiers in immunology · 2024Article
- In silico analysis reveals mir-98-5p as a potential inhibitor of tumor cell proliferation and metastasis in colorectal cancer by targeting the fzd3 receptor of the Wnt signaling pathway.Journal, genetic engineering & biotechnology · 2023Article
- An old friend with a new face: tRNA-derived small RNAs with big regulatory potential in cancer biology.British journal of cancer · 2023Review
- FZD6 Promotes Melanoma Cell Invasion but Not Proliferation by Regulating Canonical Wnt Signaling and Epithelial‒Mesenchymal Transition.The Journal of investigative dermatology · 2023Article
- Spatial cancer systems biology resolves heterotypic interactions and identifies disruption of spatial hierarchy as a pathological driver event.bioRxiv : the preprint server for biology · 2023Article
- Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Frizzled 3 receptor (FZD3) plays an important role in the homeostasis of the neural crest and its derivatives, which give rise to pigment-synthesizing cells, melanocytes. While the role for FZD3 in specification of the melanocytic lineage from neural crest is well established, its significance in the formation of melanoma, its associated malignancy, is less understood. In this study we identified FZD3 as a critical regulator of human melanoma tumorigenesis. Down-regulation of FZD3 abrogated growth, colony-forming potential, and invasive capacity of patient-derived melanoma cells. Xenotransplantation of tumor cells with down-regulated FZD3 levels originating from melanomas carrying the BRAF(V600) mutation uniformly suppressed their capacity for tumor and metastasis formation. FZD3 knockdown leads to the down-regulation of the core cell cycle protein components (cyclins D1, E2, B1, and CDKs 1, 2, and 4) in melanomas with a hyperactive BRAF oncogene, indicating a dominant role of this receptor during melanoma pathogenesis. Enriched pathway analysis revealed that FZD3 inhibits transcriptional networks controlled by CREB5, FOXD1, and ATF3, which suppress the activity of MAPK-mediated signaling. Thus, FZD3 establishes a positive-feedback mechanism that activates MAPK signal transduction network, critical to melanoma carcinogenesis. Importantly, high levels of FZD3 mRNA were found to be correlated with melanoma advancement to metastatic stages and limited patient survival. Changes in gene-expression patterns mediated by FZD3 activity occur in the absence of nuclear β-catenin function, thus representing an important therapeutic target for the melanoma patients whose disease progresses independent of canonical WNT signaling.
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