ArticleThe Journal of clinical investigation2014
WNT5A enhances resistance of melanoma cells to targeted BRAF inhibitors.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
108 citing papers in PubMed, 172 citations in OpenAlex.
- A prospective genome-wide study of prostate cancer metastases reveals association of wnt pathway activation and increased cell cycle proliferation with primary resistance to abiraterone acetate-prednisone.Annals of oncology : official journal of the European Society for Medical Oncology · 2018Trial
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- Rapid activation of ARF6 after RAF inhibition augments BRAFOncogene · 2026Article
- Catestatin peptide impedes melanoma progression and drug resistance by reprogramming oncogenic signaling pathways.Oncogenesis · 2026Article
- Wnt signaling and the tumor microenvironment: implications for cancer progression and therapeutics.Oncogene · 2026Review
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- Catestatin peptide impedes melanoma progression and drug resistance by reprogramming oncogenic signaling pathways.Research square · 2026Article
- Ubiquitin E3 ligase KPC1 governs mesenchymal metastatic melanoma reprogramming via proteasomal degradation of ZEB1.Cell death & disease · 2025Article
- Targeting the tumor cell-intrinsic ITGB2 axis inhibits melanoma progression.Molecular cancer · 2025Article
- Genetic Insight into Expression-Defined Melanoma Subtypes and Network Mechanisms: An in Silico Study.Genes · 2025Article
- Catestatin suppresses melanoma progression and drug resistance through multitargeted modulation of signaling pathways.bioRxiv : the preprint server for biology · 2025Article
- Rapid activation of ARF6 after RAF inhibition augments BRAFV600E and promotes therapy resistance.Research square · 2025Article
- Phosphorylation of KIAA1429 promotes oxaliplatin resistance through activating the FZD7-Wnt signaling in BRAFJournal of experimental & clinical cancer research : CR · 2025Article
- Oncogenic Signalling Pathways in Cancer Immunotherapy: Leader or Follower in This Delicate Dance?International journal of molecular sciences · 2025Review
- Fatty acid uptake activates an AXL-CAV1-β-catenin axis to drive melanoma progression.Genes & development · 2025Article
- A novel Frizzled 7 antibody disrupts the Wnt pathway and inhibits Wilms tumor growth.Frontiers in bioengineering and biotechnology · 2025Article
- Characterization of Wnt Signaling Pathway Aberrations in Metastatic Prostate Cancer.Molecular cancer research : MCR · 2024Article
- Review
- Review
48 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
About half of all melanomas harbor a mutation that results in a constitutively active BRAF kinase mutant (BRAF(V600E/K)) that can be selectively inhibited by targeted BRAF inhibitors (BRAFis). While patients treated with BRAFis initially exhibit measurable clinical improvement, the majority of patients eventually develop drug resistance and relapse. Here, we observed marked elevation of WNT5A in a subset of tumors from patients exhibiting disease progression on BRAFi therapy. WNT5A transcript and protein were also elevated in BRAFi-resistant melanoma cell lines generated by long-term in vitro treatment with BRAFi. RNAi-mediated reduction of endogenous WNT5A in melanoma decreased cell growth, increased apoptosis in response to BRAFi challenge, and decreased the activity of prosurvival AKT signaling. Conversely, overexpression of WNT5A promoted melanoma growth, tumorigenesis, and activation of AKT signaling. Similarly to WNT5A knockdown, knockdown of the WNT receptors FZD7 and RYK inhibited growth, sensitized melanoma cells to BRAFi, and reduced AKT activation. Together, these findings suggest that chronic BRAF inhibition elevates WNT5A expression, which promotes AKT signaling through FZD7 and RYK, leading to increased growth and therapeutic resistance. Furthermore, increased WNT5A expression in BRAFi-resistant melanomas correlates with a specific transcriptional signature, which identifies potential therapeutic targets to reduce clinical BRAFi resistance.
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Registered trials
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.