ArticlePLoS genetics2014
SPDEF inhibits prostate carcinogenesis by disrupting a positive feedback loop in regulation of the Foxm1 oncogene.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Integrative meta-analysis and experimental validation reveal the oncogenic role of SACS and its therapeutic targeting potential in colorectal cancer.Scientific reports · 2025Pooled it
- M1-NP1 interfering-peptide inhibits cancer cell proliferation and migration by targeting the transcription factor FOXM1.Journal of pharmaceutical analysis · 2026Article
- FOXM1 inhibitor, RCM‑1, enhances venetoclax mediated apoptosis through downregulation of ATP2B4 in rhabdomyosarcoma.International journal of oncology · 2026Article
- Assessing the Tumor Suppressive Impact and Regulatory Mechanisms of SPDEF Expression in Breast Cancer.Cancers · 2025Article
- Long non-coding RNA NR2F1-AS1: an increasingly significant LncRNA in human cancers.Journal of physiology and biochemistry · 2025Review
- CpG dinucleotide methylation of the SPDEF gene as a blood-based epigenetic biomarker for prostate cancer diagnosis.BMC urology · 2025Article
- Review
- Review
- In-vivo screening implicates endoribonuclease Regnase-1 in modulating senescence-associated lysosomal changes.GeroScience · 2024Article
- Review
- Oncogenic role of FOXM1 in human prostate cancer (Review).Oncology reports · 2024Review
- FOXM1: A small fox that makes more tracks for cancer progression and metastasis.Seminars in cancer biology · 2023Review
- OverexpressedJournal of thoracic disease · 2023Article
- The development of an anti-cancer peptide M1-21 targeting transcription factor FOXM1.Cell & bioscience · 2023Article
- Landscape and significance of human super enhancer-driven core transcription regulatory circuitry.Molecular therapy. Nucleic acids · 2023Article
- FOXM1: Functional Roles of FOXM1 in Non-Malignant Diseases.Biomolecules · 2023Review
- Lipogenesis promotes mitochondrial fusion and maintains cancer stemness in human NSCLC.JCI insight · 2023Article
- Mucus Hypersecretion in Chronic Obstructive Pulmonary Disease and Its Treatment.Mediators of inflammation · 2023Review
- Demonstration of Safety in Wild Type Mice of npFOXF1, a Novel Nanoparticle-Based Gene Therapy for Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins.Biologics : targets & therapy · 2023Article
- Improving anti-tumor efficacy of low-dose Vincristine in rhabdomyosarcomaFrontiers in oncology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
SAM-pointed domain-containing ETS transcription factor (SPDEF) is expressed in normal prostate epithelium. While its expression changes during prostate carcinogenesis (PCa), the role of SPDEF in prostate cancer remains controversial due to the lack of genetic mouse models. In present study, we generated transgenic mice with the loss- or gain-of-function of SPDEF in prostate epithelium to demonstrate that SPDEF functions as tumor suppressor in prostate cancer. Loss of SPDEF increased cancer progression and tumor cell proliferation, whereas over-expression of SPDEF in prostate epithelium inhibited carcinogenesis and reduced tumor cell proliferation in vivo and in vitro. Transgenic over-expression of SPDEF inhibited mRNA and protein levels of Foxm1, a transcription factor critical for tumor cell proliferation, and reduced expression of Foxm1 target genes, including Cdc25b, Cyclin B1, Cyclin A2, Plk-1, AuroraB, CKS1 and Topo2alpha. Deletion of SPDEF in transgenic mice and cultures prostate tumor cells increased expression of Foxm1 and its target genes. Furthermore, an inverse correlation between SPDEF and Foxm1 levels was found in human prostate cancers. The two-gene signature of low SPDEF and high FoxM1 predicted poor survival in prostate cancer patients. Mechanistically, SPDEF bound to, and inhibited transcriptional activity of Foxm1 promoter by interfering with the ability of Foxm1 to activate its own promoter through auto-regulatory site located in the -745/-660 bp Foxm1 promoter region. Re-expression of Foxm1 restored cellular proliferation in the SPDEF-positive cancer cells and rescued progression of SPDEF-positive tumors in mouse prostates. Altogether, SPDEF inhibits prostate carcinogenesis by preventing Foxm1-regulated proliferation of prostate tumor cells. The present study identified novel crosstalk between SPDEF tumor suppressor and Foxm1 oncogene and demonstrated that this crosstalk is required for tumor cell proliferation during progression of prostate cancer in vivo.
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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.