ArticleInternational journal of oral science2021
SPDEF suppresses head and neck squamous cell carcinoma progression by transcriptionally activating NR4A1.
Article in International journal of oral science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Phase 2 study of neoadjuvant enzalutamide and paclitaxel for luminal androgen receptor-enriched TNBC: Trial results and insights into "ARness".Cell reports. Medicine · 2024Trial
- SPDEF downregulation promotes tumor aggressiveness and poor prognosis in triple-negative breast cancer.Translational cancer research · 2026Article
- Histone lactylation-driven feedback loop modulates pyrimidine metabolism to promote oral carcinogenesis.Cell death & disease · 2026Article
- Age-dependent elevation of Nr4a1 attenuates PI3K/AKT/GSK3β pathway and mediates tau hyperphosphorylation and cognitive impairments.Journal of advanced research · 2026Article
- Integrative multi-omics analysis reveals gut-skin axis mechanisms and novel therapeutic targetmSystems · 2026Article
- Assessing the Tumor Suppressive Impact and Regulatory Mechanisms of SPDEF Expression in Breast Cancer.Cancers · 2025Article
- CRISPR/Cas9 screening reveals Zfp607b as a novel transcription factor regulating myogenesis.Genes & diseases · 2025Article
- Transcription factor ELF4 in physiology and diseases: Molecular roles and clinical implications.Genes & diseases · 2025Review
- ETS-1 in tumor immunology: implications for novel anti-cancer strategies.Frontiers in immunology · 2025Review
- SPDEF ameliorates UUO-induced renal fibrosis by transcriptional activation of NR4A1.Molecular medicine (Cambridge, Mass.) · 2024Article
- Integrative single-cell and bulk transcriptomes analyses reveals heterogeneity of serine-glycine-one-carbon metabolism with distinct prognoses and therapeutic vulnerabilities in HNSCC.International journal of oral science · 2024Article
- Review
- FoxO1 promotes ovarian cancer by increasing transcription and METTL14-mediated mCancer science · 2024Article
- Sphingosine kinase 1-specific inhibitor PF543 reduces goblet cell metaplasia of bronchial epithelium in an acute asthma model.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Inhibition of the Tumor Suppressor Gene SPINK5 via EHMT2 Induces the Oral Squamous Cell Carcinoma Development.Molecular biotechnology · 2024Article
- TTC7B is a new prognostic biomarker in head and neck squamous cell carcinoma linked to immune infiltration and ferroptosis.Cancer medicine · 2023Article
- TIPE3 represses head and neck squamous cell carcinoma progression via triggering PGAM5 mediated mitochondria dysfunction.Cell death & disease · 2023Article
- Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis.Bioactive materials · 2023Article
- BASP1 is a prognostic biomarker associated with immunotherapeutic response in head and neck squamous cell carcinoma.Frontiers in oncology · 2023Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF) plays dual roles in the initiation and development of human malignancies. However, the biological role of SPDEF in head and neck squamous cell carcinoma (HNSCC) remains unclear. In this study, the expression level of SPDEF and its correlation with the clinical parameters of patients with HNSCC were determined using TCGA-HNSC, GSE65858, and our own clinical cohorts. CCK8, colony formation, cell cycle analysis, and a xenograft tumor growth model were used to determine the molecular functions of SPDEF in HNSCC. ChIP-qPCR, dual luciferase reporter assay, and rescue experiments were conducted to explore the potential molecular mechanism of SPDEF in HNSCC. Compared with normal epithelial tissues, SPDEF was significantly downregulated in HNSCC tissues. Patients with HNSCC with low SPDEF mRNA levels exhibited poor clinical outcomes. Restoring SPDEF inhibited HNSCC cell viability and colony formation and induced G0/G1 cell cycle arrest, while silencing SPDEF promoted cell proliferation in vitro. The xenograft tumor growth model showed that tumors with SPDEF overexpression had slower growth rates, smaller volumes, and lower weights. SPDEF could directly bind to the promoter region of NR4A1 and promoted its transcription, inducing the suppression of AKT, MAPK, and NF-κB signaling pathways. Moreover, silencing NR4A1 blocked the suppressive effect of SPDEF in HNSCC cells. Here, we demonstrate that SPDEF acts as a tumor suppressor by transcriptionally activating NR4A1 in HNSCC. Our findings provide novel insights into the molecular mechanism of SPDEF in tumorigenesis and a novel potential therapeutic target for HNSCC.
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