ArticleProceedings of the National Academy of Sciences of the United States of America2012
Stromal epigenetic dysregulation is sufficient to initiate mouse prostate cancer via paracrine Wnt signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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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
52 citing papers in PubMed, 86 citations in OpenAlex.
- Canonical Wnt signaling in the regulation of prostate cancer stem cells: a key driver of castration-resistant prostate cancer and a therapeutic opportunity.Journal of translational medicine · 2026Review
- A double-negative prostate cancer subtype is vulnerable to SWI/SNF-targeting degrader molecules.bioRxiv : the preprint server for biology · 2025Article
- Stem cell-derived exosomes: a potential therapeutic strategy for enhancing tendon stem/progenitor cells function in tendon-bone healing.Journal of orthopaedic surgery and research · 2025Review
- Aged and BRCA-Mutated Stromal Cells Drive Epithelial Cell Transformation.Cancer discovery · 2025Article
- Epigenetic Regulation of Stromal and Immune Cells and Therapeutic Targets in the Tumor Microenvironment.Biomolecules · 2025Review
- Review
- Decoding high mobility group A2 protein expression regulation and implications in human cancers.Discover oncology · 2024Review
- Epigenetic-related gene-based prognostic model construction and validation in prostate adenocarcinoma.Heliyon · 2024Article
- Targeting the epigenome to reinvigorate T cells for cancer immunotherapy.Military Medical Research · 2023Review
- Metabolically regulated lineages in prostate cancer.Nature cell biology · 2023Article
- Epigenetic reprogramming during prostate cancer progression: A perspective from development.Seminars in cancer biology · 2022Review
- GIPC2 interacts with Fzd7 to promote prostate cancer metastasis by activating WNT signaling.Oncogene · 2022Article
- Lysophospholipid Mediators in Health and Disease.Annual review of pathology · 2022Review
- Epigenetics in modulating immune functions of stromal and immune cells in the tumor microenvironment.Cellular & molecular immunology · 2020Review
- Epigenetic changes in fibroblasts drive cancer metabolism and differentiation.Endocrine-related cancer · 2019Review
- Epigenetics of Bladder Cancer: Where Biomarkers and Therapeutic Targets Meet.Frontiers in genetics · 2019Review
- From genomics to functions: preclinical mouse models for understanding oncogenic pathways in prostate cancer.American journal of cancer research · 2019Review
- Bi-directional signaling by membrane-bound KitL induces proliferation and coordinates thymic endothelial cell and thymocyte expansion.Nature communications · 2018Article
- Stromal epigenetic alterations drive metabolic and neuroendocrine prostate cancer reprogramming.The Journal of clinical investigation · 2018Article
- High mobility group A2 (HMGA2) promotes EMT via MAPK pathway in prostate cancer.Biochemical and biophysical research communications · 2018Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Carcinomas most often result from the stepwise acquisition of genetic alterations within the epithelial compartment. The surrounding stroma can also play an important role in cancer initiation and progression. Given the rare frequencies of genetic events identified in cancer-associated stroma, it is likely that epigenetic changes in the tumor microenvironment could contribute to its tumor-promoting activity. We use Hmga2 (High-mobility group AT-hook 2) an epigenetic regulator, to modify prostate stromal cells, and demonstrate that perturbation of the microenvironment by stromal-specific overexpression of this chromatin remodeling protein alone is sufficient to induce dramatic hyperplasia and multifocal prostatic intraepithelial neoplasia lesions from adjacent naïve epithelial cells. Importantly, we find that this effect is predominantly mediated by increased Wnt/β-catenin signaling. Enhancement of Hmga2-induced paracrine signaling by overexpression of androgen receptor in the stroma drives frank murine prostate adenocarcinoma in the adjacent epithelial tissues. Our findings provide compelling evidence for the critical contribution of epigenetic changes in stromal cells to multifocal tumorigenesis.
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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.