ArticleOncotarget2014
Stromal TGF-β signaling induces AR activation in prostate cancer.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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
24 citing papers in PubMed, 48 citations in OpenAlex.
- Concordant RNA-protein evidence and human tissue metabolomics prioritize UPP1-associated nucleotide remodeling in prostate cancer.PloS one · 2026Article
- 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
- Blood-based detection of MMP11 as a marker of prostate cancer progression regulated by the ALDH1A1-TGF-β1 signaling mechanism.Journal of experimental & clinical cancer research : CR · 2025Article
- Hypoxic Regulation of the KLK4 Gene in two Different Prostate Cancer Cells Treated with TGF- β.Cell biochemistry and biophysics · 2024Article
- Proteomic landscape profiling of primary prostate cancer reveals a 16-protein panel for prognosis prediction.Cell reports. Medicine · 2024Article
- Regulation of PD-L1 Expression by Nuclear Receptors.International journal of molecular sciences · 2023Review
- Targeting the Akt/PI3K/mTOR signaling pathway for complete eradication of keloid disease by sunitinib.Apoptosis : an international journal on programmed cell death · 2022Article
- Cytoplasmic delivery of siRNA using human-derived membrane penetration-enhancing peptide.Journal of nanobiotechnology · 2022Article
- The Extracellular Matrix Stiffening: A Trigger of Prostate Cancer Progression and Castration Resistance?Cancers · 2022Review
- Remodelling of the tumour microenvironment by the kallikrein-related peptidases.Nature reviews. Cancer · 2022Review
- Effect of Kangquan Recipe () on BAMBI Expression in Hypothalamic-Pituitary-Prostate in Rats with Benign Prostatic Hyperplasia.Chinese journal of integrative medicine · 2021Article
- MAPK4 promotes prostate cancer by concerted activation of androgen receptor and AKT.The Journal of clinical investigation · 2021Article
- Androgens Accentuate TGF-β Dependent Erk/Smad Activation During Thoracic Aortic Aneurysm Formation in Marfan Syndrome Male Mice.Journal of the American Heart Association · 2020Article
- Prostate epithelial-specific expression of activated PI3K drives stromal collagen production and accumulation.The Journal of pathology · 2020Article
- Phospholipase C (PLC)ε Promotes Androgen Receptor Antagonist Resistance via the Bone Morphogenetic Protein (BMP)-6/SMAD Axis in a Castration-Resistant Prostate Cancer Cell Line.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Fluoride Alters Klk4 Expression in Maturation Ameloblasts through Androgen and Progesterone Receptor Signaling.Frontiers in physiology · 2017Article
- A novel highly potent trivalent TGF-β receptor trap inhibits early-stage tumorigenesis and tumor cell invasion in murine Pten-deficient prostate glands.Oncotarget · 2016Article
- LIM domain only 2 over-expression in prostate stromal cells facilitates prostate cancer progression through paracrine of Interleukin-11.Oncotarget · 2016Article
- Knockdown of lncRNA-ATB suppresses autocrine secretion of TGF-β2 by targeting ZNF217 via miR-200c in keloid fibroblasts.Scientific reports · 2016Article
- Multidisciplinary intervention of early, lethal metastatic prostate cancer: Report from the 2015 Coffey-Holden Prostate Cancer Academy Meeting.The Prostate · 2016Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
AR signaling is essential for the growth and survival of prostate cancer (PCa), including most of the lethal castration-resistant PCa (CRPC). We previously reported that TGF-β signaling in prostate stroma promotes prostate tumor angiogenesis and growth. By using a PCa/stroma co-culture model, here we show that stromal TGF-β signaling induces comprehensive morphology changes of PCa LNCaP cells. Furthermore, it induces AR activation in LNCaP cells in the absence of significant levels of androgen, as evidenced by induction of several AR target genes including PSA, TMPRSS2, and KLK4. SD-208, a TGF-β receptor 1 specific inhibitor, blocks this TGF-β induced biology. Importantly, stromal TGF-β signaling together with DHT induce robust activation of AR. MDV3100 effectively blocks DHT-induced, but not stromal TGF-β signaling induced AR activation in LNCaP cells, indicating that stromal TGF-β signaling induces both ligand-dependent and ligand-independent AR activation in PCa. TGF-β induces the expression of several growth factors and cytokines in prostate stromal cells, including IL-6, and BMP-6. Interestingly, BMP-6 and IL-6 together induces robust AR activation in these co-cultures, and neutralizing antibodies against BMP-6 and IL-6 attenuate this action. Altogether, our study strongly suggests tumor stromal microenvironment induced AR activation as a direct mechanism of CRPC.
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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.