Evidence map›Paper›PMID 33627781›Full record

ArticleOncogene2021

Nerve growth factor receptor increases the tumor growth and metastatic potential of triple-negative breast cancer cells.

Renfei Wu, Koukou Li, Mingheng Yuan, Kathy Qian Luo

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
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  11. Article
  12. Article
  13. Mesenchymal stroma drives axonogenesis and nerve-induced aggressiveness in osteosarcoma.Journal of experimental & clinical cancer research : CR · 2025
    Article
  14. ERCC1/NGFR affects prognosis in basal-like breast cancer.European journal of medical research · 2025
    Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Renfei WuFaculty of Health Sciences, University of Macau, Macao SAR, China.ORCID http://orcid.org/0000-0002-8847-7254
Koukou LiFaculty of Health Sciences, University of Macau, Macao SAR, China.
Mingheng YuanFaculty of Health Sciences, University of Macau, Macao SAR, China.
Kathy Qian LuoFaculty of Health Sciences, University of Macau, Macao SAR, China. kluo@um.edu.mo.ORCID http://orcid.org/0000-0001-7454-9547
University of Macau · MO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cellular heterogeneity and the lack of metastatic biomarkers limit the diagnosis of and development of therapies for metastatic triple-negative breast cancer (TNBC). Thus, development of new clinically relevant markers is urgently needed. By using RNA-seq analysis, we found that nerve growth factor receptor (NGFR) was highly expressed in metastatic lung clones of MDA-MB-231 cells. This high level of NGFR expression was necessary for TNBC cells to grow into tumor spheres under nonadhesive conditions, resist anoikis, promote primary tumor growth and increase metastasis in mice. NGFR was also expressed at a high level in a greater number of TNBC patients (45%) than non-TNBC patients (23%), enriched in higher grade tumors, and negatively correlated with the overall survival of TNBC patients. Mechanistic analysis indicated that NGFR exerted its prometastatic effects by binding with neurotrophic receptor tyrosine kinase 3 (TrkC) mainly through a ligand-independent manner, which activated the MEK-ERK1-ZEB1 and PI3K-AKT signaling pathways, increased the level of fibronectin, and decreased the expression of PUMA. Notably, we observed that NGFR expression in TrkC-positive metastatic clones reduced cellular sensitivity to anti-Trk therapy. Moreover, WNT family member 5a (WNT5A) and TrkC activated NGFR transcription in a ZEB1-dependent manner. Taken together, this study identified NGFR as a novel driver for transforming TNBC into higher grade metastatic tumors. Our findings provide the basis for the future development of NGFR as a diagnostic and prognostic marker for determining the metastatic potential of TNBC and as a therapeutic target for treating TNBC patients.

Indexed as

AnimalsCell ProliferationClonal EvolutionGene Expression Regulation, NeoplasticHumansLung NeoplasmsMiceMitogen-Activated Protein Kinase 3Mitogen-Activated Protein Kinase KinasesNeoplasm MetastasisNerve Tissue ProteinsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReceptors, Nerve Growth FactorReceptor, trkCRNA-SeqMAPK3 protein, humanMitogen-Activated Protein Kinase 3Mitogen-Activated Protein Kinase KinasesNerve Tissue ProteinsNGFR protein, humanNTRK3 protein, humanPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReceptors, Nerve Growth FactorReceptor, trkCWnt-5a ProteinWNT5A protein, humanZEB1 protein, humanZinc Finger E-box-Binding Homeobox 1

Identifiers

PMID33627781
OpenAlexW3129326806

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.