SPDEF suppresses head and neck squamous cell carcinoma progression by transcriptionally activating NR4A1.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34667150", "kind": "science-record", "revision": 3, "content_hash": "sha256:ffafc8879bdf00afbdef6596c3f5a389f7bae55cd482f4329c716fd98e4f60cf", "created_at": "2026-11-01T17:36:20Z", "updated_at": "2026-11-01T21:26:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "SPDEF suppresses head and neck squamous cell carcinoma progression by transcriptionally activating NR4A1.", "doi": "10.1038/s41368-021-00138-0", "pmid": "34667150", "authors": ["Yanting Wang", "Xianyue Ren", "Weiyu Li", "Ruoyan Cao", "Suyang Liu", "Laibo Jiang", "Bin Cheng", "Juan Xia"], "journal": "International journal of oral science", "year": 2021, "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.", "claims": [{"id": "claim-method", "statement": "Kaplan–Meier method was used to plot survival curves, and log-rank test was used to estimate survival rates.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34667150", "locator": "sections[21] \"Statistical analysis\" paragraph 2", "quote": "Kaplan–Meier method was used to plot survival curves, and log-rank test was used to estimate survival rates."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used and/or analyzed during the current study are contained within the manuscript or available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34667150", "locator": "sections[28] \"notes\" paragraph 1", "quote": "The data used and/or analyzed during the current study are contained within the manuscript or available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using Kaplan–Meier survival analysis of the TCGA-HNSC and GSE65858 cohorts, the study found that low SPDEF mRNA levels were associated with shorter overall survival in HNSCC patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34667150", "locator": "sections[3] \"SPDEF downregulation is associated with poor survival in HNSCC\" paragraph 2", "quote": "We analyzed the SPDEF mRNA levels in a HNSCC cohort in The Cancer Genome Atlas (TCGA) database."}, {"asset": "source:pmid:34667150", "locator": "sections[3] \"SPDEF downregulation is associated with poor survival in HNSCC\" paragraph 2", "quote": "The results showed that the expression levels of SPDEF were significantly lower in HNSCC tissues (n = 500) compared with normal epithelial tissues (n = 44) (P < 0.001, Fig. 1a)."}, {"asset": "source:pmid:34667150", "locator": "sections[3] \"SPDEF downregulation is associated with poor survival in HNSCC\" paragraph 2", "quote": "Kaplan–Meier survival analysis indicated that the overall survival times of HNSCC patients with low SPDEF mRNA levels were shorter than those of patients with high SPDEF mRNA levels (P = 0.023, Fig. 1b)."}, {"asset": "source:pmid:34667150", "locator": "sections[3] \"SPDEF downregulation is associated with poor survival in HNSCC\" paragraph 2", "quote": "Patients from a separate HNSCC dataset (GSE65858) were divided into high (n = 124) or low (n = 146) SPDEF expression groups based on the optimal cutoff value (6.416), and similar results were obtained (P = 0.018, Fig. 1c)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using Kaplan–Meier survival analysis of the TCGA-HNSC and GSE65858 cohorts, the study found that low SPDEF mRNA levels were associated with shorter overall survival in HNSCC patients.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34667150"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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