ArticleJournal of experimental & clinical cancer research : CR2021
FGF19/FGFR4 signaling axis confines and switches the role of melatonin in head and neck cancer metastasis.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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
17 citing papers in PubMed, 27 citations in OpenAlex.
- Targeting the FGF19/FGFR4 positive feedback loop to disrupt ERK-mediated tumor progression in head and neck cancer.Journal of translational medicine · 2026Article
- Melatonin in Integrative Oncology: Biological Mechanisms, Therapeutic Evidence and Implementation Strategies.Oncology research · 2026Review
- FGF19 in Solid Tumors: Molecular Mechanisms, Metabolic Reprogramming, and Emerging Therapeutic Opportunities.Theranostics · 2026Review
- Melatonin Induces PERK-ATF4 Unfolded Protein Response and Apoptosis in Human Choriocarcinoma Cells.Journal of pineal research · 2025Article
- Blocking the TCA Cycle in Cancer Cells Potentiates CD36+ T-cell-Mediated Antitumor Immunity by Suppressing ER Stress-Associated THBS2 Signaling.Cancer research · 2025Article
- The CRISPR-Cas revolution in head and neck cancer: a new era of targeted therapy.Functional & integrative genomics · 2025Review
- Melatonin: a natural guardian in cancer treatment.Frontiers in pharmacology · 2025Review
- Comprehensive analysis of endoplasmic reticulum stress related signature in head and neck squamous carcinoma.Scientific reports · 2024Article
- Antioxidant Use after Diagnosis of Head and Neck Squamous Cell Carcinoma (HNSCC): A Systematic Review of Application during Radiotherapy and in Second Primary Cancer Prevention.Antioxidants (Basel, Switzerland) · 2023Review
- Reciprocal FGF19-GLI2 signaling induces epithelial-to-mesenchymal transition to promote lung squamous cell carcinoma metastasis.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Adaptive c-Met-PLXDC2 Signaling Axis Mediates Cancer Stem Cell Plasticity to Confer Radioresistance-associated Aggressiveness in Head and Neck Cancer.Cancer research communications · 2023Article
- A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response.Frontiers in molecular neuroscience · 2023Review
- Potential of melatonin to reverse epigenetic aberrations in oral cancer: new findings.EXCLI journal · 2023Review
- Melatonin inhibits ESCC tumor growth by mitigating the HDAC7/β-catenin/c-Myc positive feedback loop and suppressing the USP10-maintained HDAC7 protein stability.Military Medical Research · 2022Article
- Usefulness of Melatonin and Other Compounds as Antioxidants and Epidrugs in the Treatment of Head and Neck Cancer.Antioxidants (Basel, Switzerland) · 2021Review
- Blockade of glutamine-dependent cell survival augments antitumor efficacy of CPI-613 in head and neck cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- Using Patient-Derived Xenografts to Explore the Efficacy of Treating Head-and-Neck Squamous Cell Carcinoma With Anlotinib.Pathology oncology research : POR · 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
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThere is no consensus about the effective dosages of melatonin in cancer management, thus, it is imperative to fully understand the dose-dependent responsiveness of cancer cells to melatonin and the underlying mechanisms.
methodsHead and neck squamous cell carcinoma (HNSCC) cells with or without melatonin treatment were used as a research platform. Gene depletion was achieved by short hairpin RNA, small interfering RNA, and CRISPR/Cas9. Molecular changes and regulations were assessed by Western blotting, quantitative RT-PCR (qRT-PCR), immunohistochemistry, and chromatin Immunoprecipitation coupled with qPCR (ChIP-qPCR). The therapeutic efficacy of FGF19/FGFR4 inhibition in melatonin-mediated tumor growth and metastasis was evaluated in orthotopic tongue tumor mice.
resultsThe effect of melatonin on controlling cell motility and metastasis varies in HNSCC cells, which is dose-dependent. Mechanistically, high-dose melatonin facilitates the upregulation of FGF19 expression through activating endoplasmic stress (ER)-associated protein kinase RNA-like endoplasmic reticulum kinase (PERK)-Eukaryotic initiation factor 2 alpha (eIF2α)-activating transcription factor 4 (ATF4) pathway, which in turn promotes FGFR4-Vimentin invasive signaling and attenuates the role of melatonin in repressing metastasis. Intriguingly, following long-term exposure to high-dose melatonin, epithelial HNSCC cells revert the process towards mesenchymal transition and turn more aggressive, which is enabled by FGF19/FGFR4 upregulation and alleviated by genetic depletion of the FGF19 and FGFR4 genes or the treatment of FGFR4 inhibitor H3B-6527.
conclusionsOur study gains novel mechanistic insights into melatonin-mediated modulation of FGF19/FGFR4 signaling in HNSCC, demonstrating that activating this molecular node confines the role of melatonin in suppressing metastasis and even triggers the switch of its function from anti-metastasis to metastasis promotion. The blockade of FGF19/FGFR4 signaling would have great potential in improving the efficacy of melatonin supplements in cancer treatment.
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.