ArticleMolecular cancer2014
Inhibition of G9a induces DUSP4-dependent autophagic cell death in head and neck squamous cell carcinoma.
Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Review
- Transcriptional and epigenetic regulation of autophagy: mechanisms, disease relevance and therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Dual-Specificity Protein Phosphatases Targeting Extracellular Signal-Regulated Kinases: Friends or Foes in the Biology of Cancer?International journal of molecular sciences · 2025Review
- Molecular insight into histone methylation as a novel target for oral squamous cell carcinoma: future hope in personalised medicine.Journal of Cancer · 2025Review
- Advances in the study of posttranslational modifications of histones in head and neck squamous cell carcinoma.Clinical epigenetics · 2024Review
- Discovery of the First-in-Class G9a/GLP PROTAC Degrader.Journal of medicinal chemistry · 2024Article
- Discovery of the First-in-class G9a/GLP PROTAC Degrader.bioRxiv : the preprint server for biology · 2024Article
- Epigenetic and post-translational modifications in autophagy: biological functions and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Silencing circFTO inhibits malignant phenotype through modulating DUSP4 expression in clear cell renal cell carcinoma.Cell death discovery · 2022Article
- Cell death as part of innate immunity: Cause or consequence?Immunology · 2021Review
- Article
- BIX-01294, a G9a inhibitor, suppresses cell proliferation by inhibiting autophagic flux in nasopharyngeal carcinoma cells.Investigational new drugs · 2021Article
- The Histone Methyltransferase Gene G9A Is Regulated by Nuclear Receptor 4A1 in Alveolar Rhabdomyosarcoma Cells.Molecular cancer therapeutics · 2021Article
- A therapeutic approach with combination of interferon-gamma and autophagy inhibitor for oral squamous cell carcinoma.American journal of cancer research · 2021Article
- Clinicopathologic significance of protein lysine methyltransferases in cancer.Clinical epigenetics · 2020Review
- The p38/MKP-1 signaling axis in oral cancer: Impact of tumor-associated macrophages.Oral oncology · 2020Review
- Frequent upregulation of G9a promotes RelB-dependent proliferation and survival in multiple myeloma.Experimental hematology & oncology · 2020Article
- EHMT2/G9a Inhibits Aortic Smooth Muscle Cell Death by Suppressing Autophagy Activation.International journal of biological sciences · 2020Article
- Protein Post-translational Modifications in Head and Neck Cancer.Frontiers in oncology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHead and neck squamous cell carcinoma (HNSCC) is a common cancer worldwide. Emerging evidence indicates that alteration of epigenetics might be a key event in HNSCC progression. Abnormal expression of histone methyltransferase G9a, which contributes to transcriptional repression of tumor suppressors, has been implicated in promoting cancerous malignancies. However, its role in HNSCC has not been previously characterized. In this study, we elucidate the function of G9a and its downstream mechanism in HNSCC.
methodsWe investigated the clinical relevance of G9a in HNSCC using immunohistochemistry (IHC) staining. In vitro cell proliferation and tumorigenesis ability of G9a-manipulated HNSCC cells were examined with MTT assays, clonogenic assays, and soft agar assays. We examined different routes of cell death in HNSCC cells induced by G9a-depletion or enzymatic inhibition by immunoblot, flow cytometry, fluorescent and transmission electron microscopy analysis. Specific targets of G9a were identified by affymetrix microarray and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Lastly, functions of G9a in vivo were confirmed with a xenograft tumor model.
resultsG9a expression is positively correlated to proliferation marker Ki-67 and to poor prognosis in HNSCC patients. Genetic or pharmacological inhibition of G9a reduced cell proliferation without inducing necrosis or apoptosis. Instead, autophagic cell death was the major consequence, and our investigation of mechanisms suggested it is mediated via the dual specificity phosphatase-4 (DUSP4) dependent ERK inactivation pathway. An orthotopic tumor model further confirmed the growth inhibiting effect and induction of autophagy that followed suppression of G9a.
conclusionsIn this study, we provide evidence that G9a confers the survival advantage of HNSCC. Genetic or pharmacological inhibition of G9a induces autophagic cell death; this finding provides a basis for new therapeutic targets for treating HNSCC.
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.