ArticleCarcinogenesis2014
The FGFR/MEK/ERK/brachyury pathway is critical for chordoma cell growth and survival.
Article in Carcinogenesis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Targeted Therapy for Chordoma: Key Molecular Signaling Pathways and the Role of Multimodal Therapy.Targeted oncology · 2021Pooled it
- Fine-tuning ERK activity enables proliferation-differentiation balance during lineage specification of human embryonic stem cells.PLoS biology · 2026Article
- Brachyury and IGF1R: potential opposing roles in pediatric thyroid nodular pathology.Journal of endocrinological investigation · 2025Article
- Review
- Design of an In Vitro Model for Epithelial-to-Mesenchymal Transition in Gastric Cancer.Biochemical genetics · 2025Article
- Fibroblast growth factor receptor alterations and resistance mechanisms in the treatment of pediatric solid tumors.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Chordoma: Genetics and Contemporary Management.International journal of molecular sciences · 2024Review
- Chordoma: demographics and survival analysis with a focus on racial disparities and the role of surgery, a U.S. population-based study.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Exceptionally giant neglected sacral chordoma in a post-poliotic residual paralysis patient - a rare case scenario.American journal of neurodegenerative disease · 2024Article
- Conserved enhancers control notochord expression of vertebrate Brachyury.Nature communications · 2023Article
- Brachyury-targeted immunotherapy combined with gemcitabine against head and neck cancer.Cancer immunology, immunotherapy : CII · 2023Article
- MAPK inhibitor sensitivity scores predict sensitivity driven by the immune infiltration in pediatric low-grade gliomas.Nature communications · 2023Article
- Virus-like particle-based delivery of Cas9/guide RNA ribonucleoprotein efficiently edits the brachyury gene and inhibits chordoma growth in vivo.Discover oncology · 2023Article
- The role of tumor immune microenvironment in chordoma: promising immunotherapy strategies.Frontiers in immunology · 2023Review
- Receptor Tyrosine Kinase Inhibitors for the Treatment of Recurrent and Unresectable Bone Sarcomas.International journal of molecular sciences · 2022Review
- Advancement of PI3 Kinase Inhibitor Combination Therapies for PI3K-Aberrant Chordoma.Journal of neurological surgery. Part B, Skull base · 2022Article
- Bibliometric analysis of the global research trends and hotspots in chordoma from 2000 to 2020.PloS one · 2022Article
- Emerging target discovery and drug repurposing opportunities in chordoma.Frontiers in oncology · 2022Review
- Drug combination screening as a translational approach toward an improved drug therapy for chordoma.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- Multiple malignant tumors in a patient with familial chordoma, a case report.BMC medical genomics · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Recent evidence suggests that the expression of brachyury is necessary for chordoma growth. However, the mechanism associated with brachyury-regulated cell growth is poorly understood. Fibroblast growth factor (FGF), a regulator of brachyury expression in normal tissue, may also play an important role in chordoma pathophysiology. Using a panel of chordoma cell lines, we explored the role of FGF signaling and brachyury in cell growth and survival. Western blots showed that all chordoma cell lines expressed fibroblast growth factor receptor 2 (FGFR2), FGFR3, mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK), whereas no cell lines expressed FGFR1 and FGFR4. Results of enzyme-linked immunosorbent assay indicated that chordoma cells produced FGF2. Neutralization of FGF2 inhibited MEK/ERK phosphorylation, decreased brachyury expression and induced apoptosis while reducing cell growth. Activation of the FGFR/MEK/ERK/brachyury pathway by FGF2-initiated phosphorylation of FGFR substrate 2 (FRS2)-α (Tyr196) prevented apoptosis while promoting cell growth and epithelial-mesenchymal transition (EMT). Immunofluorescence staining showed that FGF2 promoted the translocation of phosphorylated ERK to the nucleus and increased brachyury expression. The selective inhibition of FGFR, MEK and ERK phosphorylation by PD173074, PD0325901 and PD184352, respectively, decreased brachyury expression, induced apoptosis, and inhibited cell growth and EMT. Moreover, knockdown of brachyury by small hairpin RNA reduced FGF2 secretion, inhibited FGFR/MEK/ERK phosphorylation and blocked the effects of FGF2 on cell growth, apoptosis and EMT. Those findings highlight that FGFR/MEK/ERK/brachyury pathway coordinately regulates chordoma cell growth and survival and may represent a novel chemotherapeutic target for chordoma.
Indexed as
Identifiers
What OpenQuestion holds
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.