ArticleOncotarget2015
NGF-induced TrkA/CD44 association is involved in tumor aggressiveness and resistance to lestaurtinib.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 36 citations in OpenAlex.
- TrkA activation sustains chemotherapy resistance in chemotolerant medulloblastoma cells.Acta neuropathologica communications · 2026Article
- NGF-mediated tumor-stroma crosstalk promotes prostate cancer aggressiveness.Journal of translational medicine · 2026Article
- Article
- Review
- ProNGF promotes brain metastasis through TrkA/EphA2 induced Src activation in triple negative breast cancer cells.Experimental hematology & oncology · 2023Article
- β-Lapachone Exerts Anticancer Effects by Downregulating p53, Lys-Acetylated Proteins, TrkA, p38 MAPK, SOD1, Caspase-2, CD44 and NPM in Oxaliplatin-Resistant HCT116 Colorectal Cancer Cells.International journal of molecular sciences · 2023Article
- TrkA Co-Receptors: The Janus Face of TrkA?Cancers · 2023Review
- Review
- Anticancer Effect of Cathelicidin LL-37, Protegrin PG-1, Nerve Growth Factor NGF, and Temozolomide: Impact on the Mitochondrial Metabolism, Clonogenic Potential, and Migration of Human U251 Glioma Cells.Molecules (Basel, Switzerland) · 2022Article
- Direct interaction of TrkA/CD44v3 is essential for NGF-promoted aggressiveness of breast cancer cells.Journal of experimental & clinical cancer research : CR · 2022Article
- Article
- Regulation of Eosinophil Recruitment and Allergic Airway Inflammation by Tropomyosin Receptor Kinase A.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Tumour innervation and neurosignalling in prostate cancer.Nature reviews. Urology · 2020Review
- TGFβ2-induced formation of lipid droplets supports acidosis-driven EMT and the metastatic spreading of cancer cells.Nature communications · 2020Article
- Cancer stem cells-driven tumor growth and immune escape: the Janus face of neurotrophins.Aging · 2019Article
- Up-regulated GGA3 promotes non-small cell lung cancer proliferation by regulating TrkA receptor.Translational cancer research · 2019Article
- Cytokine Signaling in Tumor Progression.Immune network · 2017Review
- Nerve growth factor modulates the tumor cells migration in ovarian cancer through the WNT/β-catenin pathway.Oncotarget · 2016Article
- Trk inhibition reduces cell proliferation and potentiates the effects of chemotherapeutic agents in Ewing sarcoma.Oncotarget · 2016Article
- Neurotrophin signaling in cancer stem cells.Cellular and molecular life sciences : CMLS · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is accumulating evidence that TrkA and its ligand Nerve Growth Factor (NGF) are involved in cancer development. Staurosporine derivatives such as K252a and lestaurtinib have been developed to block TrkA kinase signaling, but no clinical trial has fully demonstrated their therapeutic efficacy. Therapeutic failures are likely due to the existence of intrinsic signaling pathways in cancer cells that impede or bypass the effects of TrkA tyrosine kinase inhibitors. To verify this hypothesis, we combined different approaches including mass spectrometry proteomics, co-immunoprecipitation and proximity ligation assays. We found that NGF treatment induced CD44 binding to TrkA at the plasma membrane and subsequent activation of the p115RhoGEF/RhoA/ROCK1 pathway to stimulate breast cancer cell invasion. The NGF-induced CD44 signaling was independent of TrkA kinase activity. Moreover, both TrkA tyrosine kinase inhibition with lestaurtinib and CD44 silencing with siRNA inhibited cell growth in vitro as well as tumor development in mouse xenograft model; combined treatment significantly enhanced the antineoplastic effects of either treatment alone. Altogether, our results demonstrate that NGF-induced tyrosine kinase independent TrkA signaling through CD44 was sufficient to maintain tumor aggressiveness. Our findings provide an alternative mechanism of cancer resistance to lestaurtinib and indicate that dual inhibition of CD44 and TrkA tyrosine kinase activity may represent a novel therapeutic strategy.
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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.