ArticleJournal of experimental & clinical cancer research : CR2022
Direct interaction of TrkA/CD44v3 is essential for NGF-promoted aggressiveness of breast cancer cells.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Expression and Signaling Pathways of Nerve Growth Factor (NGF) and Pro-NGF in Breast Cancer: A Systematic Review.Current oncology (Toronto, Ont.) · 2022Pooled it
- Spatial organization of the TNBC tumor microenvironment: multicellular niches, T-cell bottlenecks, and therapeutic opportunities.Journal of translational medicine · 2026Review
- Neural regulation of cancer: from synaptic integration to neuro-immune regulation.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- The neuroimmune axis in breast cancer: from mechanistic insights to clinical applications.BMC medicine · 2026Review
- Insight into the potential significance of miR-760 and miR-1973 in breast cancer: a comprehensive analysis.Scientific reports · 2026Article
- Natural Medicines Modulating Tumor Perineural Invasion: Regulatory Mechanisms and Therapeutic Potential.Drug design, development and therapy · 2026Review
- Nerve growth factor: what can surgeons and oncologists learn from a neurological and psychological biomarker?Molecular medicine (Cambridge, Mass.) · 2025Review
- Tumor-infiltrating nerves: unraveling the role of cancer neuroscience in tumorigenesis, disease progression, and emerging therapies.Discover oncology · 2025Review
- RNA splicing: Novel star in pulmonary diseases with a treatment perspective.Acta pharmaceutica Sinica. B · 2025Review
- Targeting CD44 and other pleiotropic co-receptors as a means for broad inhibition of tumor growth and metastasis.Clinical & experimental metastasis · 2024Review
- VX-509 attenuates the stemness characteristics of colorectal cancer stem-like cells by regulating the epithelial-mesenchymal transition through Nodal/Smad2/3 signaling.World journal of stem cells · 2024Article
- ProNGF promotes brain metastasis through TrkA/EphA2 induced Src activation in triple negative breast cancer cells.Experimental hematology & oncology · 2023Article
- TrkA Co-Receptors: The Janus Face of TrkA?Cancers · 2023Review
- What is the potential impact of genetic divergence of plastid ribosomal genes betweenFrontiers in plant science · 2023Article
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCD44 is a multifunctional membrane glycoprotein. Through its heparan sulfate chain, CD44 presents growth factors to their receptors. We have shown that CD44 and Tropomyosin kinase A (TrkA) form a complex following nerve growth factor (NGF) induction. Our study aimed to understand how CD44 and TrkA interact and the consequences of inhibiting this interaction regarding the pro-tumoral effect of NGF in breast cancer.
methodsAfter determining which CD44 isoforms (variants) are involved in forming the TrkA/CD44 complex using proximity ligation assays, we investigated the molecular determinants of this interaction. By molecular modeling, we isolated the amino acids involved and confirmed their involvement using mutations. A CD44v3 mimetic peptide was then synthesized to block the TrkA/CD44v3 interaction. The effects of this peptide on the growth, migration and invasion of xenografted triple-negative breast cancer cells were assessed. Finally, we investigated the correlations between the expression of the TrkA/CD44v3 complex in tumors and histo-pronostic parameters.
resultsWe demonstrated that isoform v3 (CD44v3), but not v6, binds to TrkA in response to NGF stimulation. The final 10 amino acids of exon v3 and the TrkA H112 residue are necessary for the association of CD44v3 with TrkA. Functionally, the CD44v3 mimetic peptide impairs not only NGF-induced RhoA activation, clonogenicity, and migration/invasion of breast cancer cells in vitro but also tumor growth and metastasis in a xenograft mouse model. We also detected TrkA/CD44v3 only in cancerous cells, not in normal adjacent tissues.
conclusionCollectively, our results suggest that blocking the CD44v3/TrkA interaction can be a new therapeutic option for triple-negative breast cancers.
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