ArticleCell death & disease2022
Targeting HIC1/TGF-β axis-shaped prostate cancer microenvironment restrains its progression.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 53 citations in OpenAlex.
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- C-MYC as a key effector of WNT, PI3K/AKT, MAPK, and TGF-β signaling pathways in regulation of epithelial-mesenchymal transition during tumor metastasis.Cancer cell international · 2026Review
- ANKRD49 promotes the epithelial-mesenchymal transition of non-small cell lung cancer via the PKNOX1/TGF-β1/SMAD axis.Cancer cell international · 2026Article
- TGF-β in tumor development and progression: mechanisms and therapeutics.Molecular biomedicine · 2026Review
- Targeting senescent EGR1Cell reports. Medicine · 2026Article
- Integrative analysis reveals PRKCB and SRD5A2 as potential immune-associated biomarkers in prostate cancer targeted by traditional Chinese medicine.Frontiers in oncology · 2026Article
- Dopamine agonist-associated fibrosis in prolactinomas: clinical challenges, impacts on the tumor microenvironment, and future directions.Frontiers in endocrinology · 2026Review
- TGF-beta promotes human T follicular helper cell stemness properties at the expense of effector function.Frontiers in immunology · 2026Article
- A Metastasis-competent CAF Subpopulation Defined byRecent patents on anti-cancer drug discovery · 2026Article
- Targeting Cancer-Associated Fibroblasts in Prostate Cancer: Recent Advances and Therapeutic Opportunities.Cancers · 2025Review
- Emerging role of HIC1 in prostate cancer progression and therapeutic response: A novel perspective.Journal of cell communication and signaling · 2025Article
- Pathological significance and therapeutic prospects ofCell adhesion & migration · 2025Article
- Ferroptosis meets cancer immunotherapy: Overcoming the crosstalk challenges through advanced drug delivery strategies.Acta pharmaceutica Sinica. B · 2025Review
- WGCNA-identified COL13A1 drives osteosarcoma metastasis and progression via TGF-β signaling.Journal of bone oncology · 2025Article
- Neoadjuvant immunotherapy in squamous cell carcinoma of the head and neck: current evidence and future perspectives.Molecular cancer · 2025Review
- Anti-tumor activity of CDYL2b in prostate cancer.Cancer letters · 2025Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prostate cancer (PCa) is a malignant tumor that seriously threatens men's health worldwide. Recently, stromal cells in the tumor microenvironment (TME) have been reported to contribute to the progression of PCa. However, the role and mechanism of how PCa cells interact with stromal cells to reshape the TME remain largely unknown. Here, using a spontaneous prostate adenocarcinoma (PRAD) model driven by the loss of Pten and Hic1, we found that M2 macrophages markedly infiltrated the stroma of Pten and Hic1 double conditional knockout (dCKO) mice compared with those in control (Ctrl) mice due to higher TGF-β levels secreted by HIC1-deleted PCa cells. Mechanistically, TGF-β in TME promoted the polarization of macrophages into "M2" status by activating the STAT3 pathway and modulating c-Myc to upregulate CXCR4 expression. Meanwhile, TGF-β activated the fibroblasts to form cancer-associated fibroblasts (CAFs) that secrete higher CXCL12 levels, which bound to its cognate receptor CXCR4 on M2 macrophages. Upon interaction with CAFs, M2 macrophages secreted more CXCL5, which promoted the epithelial-mesenchymal transition (EMT) of PCa via CXCR2. Moreover, using the TGF-β receptor I antagonist, galunisertib, significantly inhibited the tumor growth and progression of the TRAMP-C1 cell line-derived subcutaneous tumor model. Finally, we confirmed that the stromal microenvironment was shaped by TGF-β in HIC1-deficient PCa and was associated with the progression of PCa.
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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.