ArticleiScience2021
Multiple pathways coordinating reprogramming of endothelial cells into osteoblasts by BMP4.
Article in iScience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Spatial immune profiling of bone-metastatic castration-resistant prostate cancer reveals radium-223 immunomodulates the bone-tumor microenvironment.Prostate cancer and prostatic diseases · 2026Article
- ACTC1 promotes tumor progression by upregulating BMP4 expression in prostate cancer.BMC cancer · 2025Article
- Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.Signal transduction and targeted therapy · 2025Review
- Molecular mechanisms and targeted therapy for the metastasis of prostate cancer to the bones (Review).International journal of oncology · 2024Review
- Prostate cancer-induced endothelial-cell-to-osteoblast transition drives immunosuppression in the bone-tumor microenvironment through Wnt pathway-induced M2 macrophage polarization.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The regulatory process and practical significance of non-coding RNA in the dissemination of prostate cancer to the skeletal system.Frontiers in oncology · 2024Review
- Article
- Article
- Cancer-Associated Fibroblast Heterogeneity, Activation and Function: Implications for Prostate Cancer.Biomolecules · 2022Review
- The road of NSCLC stem cells toward bone metastases.Bone reports · 2022Article
- Review
- Retinoic Acid Receptor Activation Reduces Metastatic Prostate Cancer Bone Lesions by Blocking the Endothelial-to-Osteoblast Transition.Cancer research · 2022Article
- Prostate tumor-induced stromal reprogramming generates Tenascin C that promotes prostate cancer metastasis through YAP/TAZ inhibition.Oncogene · 2022Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Cell type transition occurs during normal development and under pathological conditions. In prostate cancer bone metastasis, prostate cancer-secreted BMP4 induces endothelial cell-to-osteoblast (EC-to-OSB) transition. Such tumor-induced stromal reprogramming supports prostate cancer progression. We delineate signaling pathways mediating EC-to-OSB transition using EC lines 2H11 and SVR. We found that BMP4-activated pSmad1-Notch-Hey1 pathway inhibits EC migration and tube formation. BMP4-activated GSK3β-βcatenin-Slug pathway stimulates Osx expression. In addition, pSmad1-regulated Dlx2 converges with the Smad1 and β-catenin pathways to stimulate osteocalcin expression. By co-expressing Osx, Dlx2, Slug and Hey1, we were able to achieve EC-to-OSB transition, leading to bone matrix mineralization in the absence of BMP4. In human prostate cancer bone metastasis specimens and MDA-PCa-118b and C4-2b-BMP4 osteogenic xenografts, immunohistochemical analysis showed that β-catenin and pSmad1 are detected in activated osteoblasts rimming the tumor-induced bone. Our results elucidated the pathways and key molecules coordinating prostate cancer-induced stromal programming and provide potential targets for therapeutic intervention.
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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.