ArticleProceedings of the National Academy of Sciences of the United States of America2009
A t-butyloxycarbonyl-modified Wnt5a-derived hexapeptide functions as a potent antagonist of Wnt5a-dependent melanoma cell invasion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 145 citations in OpenAlex.
- Fusobacterium nucleatum promotes senescence of human oral mucosa fibroblasts via the Wnt5A/mTOR pathway.Odontology · 2026Article
- DOCK1 inhibitor Box5 (TFA) suppresses proliferation of AML cell lines and prolongs survival in AML xenograft models.Scientific reports · 2026Article
- Single-Cell Atlas of Subchondral Bone Marrow Lesions Reveals Proteostasis Dysfunction as a Druggable Mechanism for Early Osteoarthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Particulate matter 2.5 promotes bladder cancer cell migration and invasion through the crosstalk between integrin-mediated MAPK/ERK and Wnt/β-catenin pathways.Particle and fibre toxicology · 2026Article
- Microfluidic chip-integrated vascularized endometrial complexes: Mitochondrial function and paracrine crosstalk enhance regenerative potential.Bioactive materials · 2025Article
- Genetic Insight into Expression-Defined Melanoma Subtypes and Network Mechanisms: An in Silico Study.Genes · 2025Article
- Spatially organized cellular communities shape functional tissue architecture in the pancreas.Science advances · 2025Article
- Targeting WNT5A noncanonical signaling attenuates renal fibrosis progression in acute kidney injury.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Regulatory effect of Wnt signaling on mitochondria in cancer: from mechanism to therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- Single-nucleus and spatial landscape of the sub-ventricular zone in human glioblastoma.Cell reports · 2025Article
- DPP an extracellular matrix molecule induces Wnt5a mediated signaling to promote the differentiation of adult stem cells into odontogenic lineage.Scientific reports · 2024Article
- WNT5A is a putative epi-driver of prostate cancer metastasis to the bone.Cancer medicine · 2024Article
- Wnt5a/β-catenin-mediated epithelial-mesenchymal transition: a key driver of subretinal fibrosis in neovascular age-related macular degeneration.Journal of neuroinflammation · 2024Article
- Heterozygous missense variant in GLI2 impairs human endocrine pancreas development.Nature communications · 2024Article
- Altered binding affinity of SIX1-Q177R correlates with enhanced WNT5A and WNT pathway effector expression in Wilms tumor.Disease models & mechanisms · 2023Article
- cRel and Wnt5a/Frizzled 5 Receptor-Mediated Inflammatory Regulation Reveal Novel Neuroprotectin D1 Targets for Neuroprotection.Cellular and molecular neurobiology · 2023Article
- ModifiedFrontiers in molecular biosciences · 2023Article
- Inhibition of Metastasis by Polypyridyl Ru(II) Complexes through Modification of Cancer Cell Adhesion -Journal of medicinal chemistry · 2022Article
- Wnt signaling in colorectal cancer: pathogenic role and therapeutic target.Molecular cancer · 2022Review
- Noncanonical Wnt5a/JNK Signaling Contributes to the Development of D-Gal/LPS-Induced Acute Liver Failure.Inflammation · 2022Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The influential role of Wnt5a in tumor progression underscores the requirement for developing molecules that can target Wnt5a-mediated cellular responses. In the aggressive skin cancer, melanoma, elevated Wnt5a expression promotes cell motility and drives metastasis. Two approaches can be used to counteract these effects: inhibition of Wnt5a expression or direct blockade of Wnt5a signaling. We have investigated both options in the melanoma cell lines, A2058 and HTB63. Both express Frizzled-5, which has been implicated as the receptor for Wnt5a in melanoma cells. However, only the HTB63 cell line expresses and secretes Wnt5a. In these cells, the cytokine, TGFbeta1, controlled the expression of Wnt5a, but due to the unpredictable effects of TGFbeta1 signaling on melanoma cell motility, targeting Wnt5a signaling via TGFbeta1 was an unsuitable strategy to pursue. We therefore attempted to target Wnt5a signaling directly. Exogenous Wnt5a stimulation of A2058 cells increased adhesion, migration and invasion, all crucial components of tumor metastasis, and the Wnt5a-derived N-butyloxycarbonyl hexapeptide (Met-Asp-Gly-Cys-Glu-Leu; 0.766 kDa) termed Box5, abolished these responses. Box5 also inhibited the basal migration and invasion of Wnt5a-expressing HTB63 melanoma cells. Box5 antagonized the effects of Wnt5a on melanoma cell migration and invasion by directly inhibiting Wnt5a-induced protein kinase C and Ca(2+) signaling, the latter of which we directly demonstrate to be essential for cell invasion. The Box5 peptide directly inhibits Wnt5a signaling, representing an approach to anti-metastatic therapy for otherwise rapidly progressive melanoma, and for other Wnt5a-stimulated invasive cancers.
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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.