ArticleOncogene2017
FOXA1 inhibits prostate cancer neuroendocrine differentiation.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 2 of them syntheses 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
97 citing papers in PubMed, 2 syntheses or guidelines pooled it, 151 citations in OpenAlex.
- Endocrine and paracrine characteristics of neuroendocrine prostate cancer.Frontiers in endocrinology · 2022Pooled it
- Neuroendocrine cells of prostate cancer: biologic functions and molecular mechanisms.Asian journal of andrologyPooled it
- Clinical and Genomic Characterization of Treatment-Emergent Small-Cell Neuroendocrine Prostate Cancer: A Multi-institutional Prospective Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Trial
- Multi-omics dissection of FOXA1 reveals cancer-type-specific transcriptional networks and functional risk variants.iScience · 2026Article
- FOXA1 is a highly sensitive diagnostic marker for prostate cancer including small cell carcinoma of the prostate.Histopathology · 2026Article
- A comprehensive pharmacological survey across heterogeneous patient-derived glioblastoma stem cell models.iScience · 2026Article
- CAF-derived PTGDS drives pancreatic cancer neuroendocrine differentiation and chemoresistance via PAQR9-MAPK.Oncogenesis · 2026Article
- FOXA1 loss drives basal/squamous de-differentiation of prostate cancer and induces an immunosuppressive tumor microenvironment.Nature communications · 2026Article
- Genetic and epigenetic mechanisms underlying treatment-induced neuroendocrine prostate cancer.Journal of the National Cancer Center · 2026Review
- Alterations in AR-FOXA1 signaling in prostate cancer progression and therapeutic resistance.Journal of the National Cancer Center · 2026Review
- The Quartet of Core Oncogenic Drivers in Neuroendocrine Prostate Cancer: Multi-Omics Dataset Integration to Forge a Translational Link Between Biology and Precision Therapy.International journal of biological sciences · 2026Review
- Molecular mechanisms and classification of castration-resistant prostate cancer: Insights into androgen receptor, cancer stem cells, and neuroendocrine features.Current urology · 2026Article
- Pan-cancer analysis reveals netrin-1 receptors as potential tumor biomarkers and immune-related therapeutic targets.Scientific reports · 2025Article
- NKX2-1 drives neuroendocrine transdifferentiation of prostate cancer via epigenetic and 3D chromatin remodeling.Nature genetics · 2025Article
- The role of transcription factors in prostate cancer progression.Molecules and cells · 2025Review
- Deciphering Complexity: The Molecular Landscape of Castration-Resistant Prostate Cancer.Surgical pathology clinics · 2025Review
- FoxA1 knockdown promotes BMSC osteogenesis in part by activating the ERK1/2 signaling pathway and preventing ovariectomy-induced bone loss.Scientific reports · 2025Article
- Immunophenotyping of colon cancer for identification of potential antigens for colon cancer vaccines.Frontiers in oncology · 2025Article
- Small cell lung cancer and prostate cancer cells with varying neuroendocrine differentiation markers show sensitivity to imipridone ONC201/TIC10.American journal of translational research · 2025Article
- The role of neuroendocrine differentiation in treatment resistance of prostate cancer and intervention strategies.Frontiers in oncology · 2025Review
37 more citing papers are in PubMed but not listed here.
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 2 institutions in 2 countries.
Funding
Abstract
Neuroendocrine prostate cancer (NEPC) has increasingly become a clinical challenge. The mechanisms by which neuroendocrine (NE) cells arises from prostate adenocarcinoma cells are poorly understood. FOXA1 is a transcription factor of the forkhead family that is required for prostate epithelial differentiation. In this study, we demonstrated that FOXA1 loss drives NE differentiation, demarcated by phenotypical changes and NEPC marker expressions. Mechanistically, this is mediated by FOXA1 binding to the promoter of interleukin 8 (IL-8), a chemokine previously shown elevated in NEPC, to directly inhibit its expression. Further, IL-8 upregulation activates the MAPK/ERK pathway, leading to ERK phosphorylation and enolase 2 (ENO2) expression. IL-8 knockdown or ERK inhibition, on the other hand, abolished FOXA1 loss-induced NE differentiation. Analysis of xenograft mouse models confirmed FOXA1 loss in NEPC tumors relative to its adenocarcinoma counterparts. Importantly, FOXA1 is downregulated in human NEPC tumors compared to primary and castration-resistant prostate cancers, and its expression is negatively correlated with that of ENO2. These findings indicate that FOXA1 transcriptionally suppresses IL-8, the expression of which would otherwise stimulate the MAPK/ERK pathway to promote NE differentiation of prostate cancer cells. Our data strongly suggest that FOXA1 loss may play a significant role in enabling prostate cancer progression to NEPC, whereas IL-8 and MAPK/ERK pathways may be promising targets for therapeutic intervention.
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.