ArticleThe Journal of clinical investigation2019
Targeting FOXA1-mediated repression of TGF-β signaling suppresses castration-resistant prostate cancer progression.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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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
113 citing papers in PubMed, 167 citations in OpenAlex.
- Evaluating Immune Checkpoint Blockade in Metastatic Castration-Resistant Prostate Cancers with Deleterious CDK12 Alterations in the Phase 2 IMPACT Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Multi-omics dissection of FOXA1 reveals cancer-type-specific transcriptional networks and functional risk variants.iScience · 2026Article
- SNAI1 ablation alters integrin-mediated adhesion and endocytic fate.Cell death & disease · 2026Article
- FOXA1 is a highly sensitive diagnostic marker for prostate cancer including small cell carcinoma of the prostate.Histopathology · 2026Article
- Morphomechanically-Informed Spatial Curvature Sequencing in Prostate Cancer.bioRxiv : the preprint server for biology · 2026Article
- SOX10-mediated regulation of the MiR-106a/363 cluster drives RAF inhibitor resistance in BRAF-mutant melanoma.Cellular and molecular life sciences : CMLS · 2026Article
- A ligandable PNT domain establishes ERG as a directly targetable oncogenic driver in prostate cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Histone methyltransferase KMT2D promotes castration-resistant prostate cancer progression by reactivating AR through FOXA1.Oncogene · 2026Article
- Integrative Proteogenomic Characterization of Left-Sided and Right-Sided Colorectal Cancer.MedComm · 2026Article
- FOXA1 loss drives basal/squamous de-differentiation of prostate cancer and induces an immunosuppressive tumor microenvironment.Nature communications · 2026Article
- Transcriptional and epigenetic reprogramming, lineage plasticity and therapy resistance in prostate cancer.Journal of the National Cancer Center · 2026Review
- Identify the PANoptosis signature and prognostic model via a multimachine-learning computational framework for bladder urothelial carcinoma.Cancer cell international · 2026Article
- Emerging therapies to overcome antiandrogen resistance and beyond in lethal prostate cancer.Journal of the National Cancer Center · 2026Review
- Genetic and epigenetic mechanisms underlying treatment-induced neuroendocrine prostate cancer.Journal of the National Cancer Center · 2026Review
- Cancer-Associated Fibroblasts in Prostate Cancer: Unraveling Mechanisms and Therapeutic Implications.Oncology research · 2026Review
- The ATM inhibitor KU55933 inhibits TGF-β1-mediated epithelial to mesenchymal transition in colorectal cancer cells.Frontiers in oncology · 2026Article
- Tumor-associated macrophages and lineage plasticity in prostate cancer: from established myeloid programs to emerging spatial hypotheses.Frontiers in immunology · 2026Review
- Radiogenomic Profiling of Prostate Tumors prior to External Beam Radiotherapy Converges on a Transcriptomic Signature of TGF-β Activity Driving Tumor Recurrence.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Observational
- Genomic alterations and associated outcomes in patients with PSMA-positive metastatic castration-resistant prostate cancer treated with 177Lu-PSMA-617.The oncologist · 2025Article
- Synergistic targeting strategies for prostate cancer.Nature reviews. Urology · 2025Review
53 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Prostate cancer (PC) progressed to castration resistance (CRPC) is a fatal disease. CRPC tumors develop resistance to new-generation antiandrogen enzalutamide through lineage plasticity, characterized by epithelial-mesenchymal transition (EMT) and a basal-like phenotype. FOXA1 is a transcription factor essential for epithelial lineage differentiation. Here, we demonstrate that FOXA1 loss leads to remarkable upregulation of transforming growth factor beta 3 (TGFB3), which encodes a ligand of the TGF-β pathway. Mechanistically, this is due to genomic occupancy of FOXA1 on an upstream enhancer of the TGFB3 gene to directly inhibit its transcription. Functionally, FOXA1 downregulation induces TGF-β signaling, EMT, and cell motility, which is effectively blocked by the TGF-β receptor I inhibitor galunisertib (LY2157299). Tissue microarray analysis confirmed reduced levels of FOXA1 protein and a concordant increase in TGF-β signaling, indicated by SMAD2 phosphorylation, in CRPC as compared with primary tumors. Importantly, combinatorial LY2157299 treatment sensitized PC cells to enzalutamide, leading to synergistic effects in inhibiting cell invasion in vitro and xenograft CRPC tumor growth and metastasis in vivo. Therefore, our study establishes FOXA1 as an important regulator of lineage plasticity mediated in part by TGF-β signaling, and supports a novel therapeutic strategy to control lineage switching and potentially extend clinical response to antiandrogen therapies.
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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.