ArticleOncogene2019
Prostate cancer promotes a vicious cycle of bone metastasis progression through inducing osteocytes to secrete GDF15 that stimulates prostate cancer growth and invasion.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 99 citations in OpenAlex.
- Spatial Mapping of the Precancer-to-Cancer Transition in Breast and Prostate.Cancer discovery · 2026Article
- Osteocyte-Derived GDF15 Promotes Paclitaxel Resistance, Tumor Growth, and Bone Microenvironment Regulation in Prostate Cancer.Current issues in molecular biology · 2026Article
- Structure-guided identification of small molecules potentially able to modulate GDF15 activity.Scientific reports · 2026Article
- High RMI1 expression is associated with cancer cell progression and poor prognosis in prostate cancer.Oncology reports · 2026Article
- The Role of GDF-15 in Heart Failure and Biomarker Potential-From Basic Science to Clinical Praxis.Biology · 2026Review
- SENP3 drives colorectal cancer progression by enhancing GDF15 expression.International journal of colorectal disease · 2026Article
- Induced Tumor-Suppressing (iTS) Cell-Based Approach for Protecting the Bone from Advanced Prostate Cancer.Biomolecules · 2026Article
- Review
- Review
- Nanoparticles Targeting the Tumor Microenvironment for the Treatment of Osteosarcoma: Recent Progress and Perspectives.International journal of nanomedicine · 2026Review
- Total flavonoids of litchi seed inhibit breast cancer metastasis by regulating the PI3K/AKT/mTOR and MAPKs signaling pathways.Pharmaceutical biology · 2025Article
- Interplay of IL-6, GDF-15 and Sarcopenia in Patients With Bladder Cancer Undergoing Radical Cystectomy and Its Implications on Survival.Journal of cachexia, sarcopenia and muscle · 2025Article
- The upregulation of GDF15 is controlled epigenetically by oncogenic TCF19 signaling in human hepatocellular carcinoma.iScience · 2025Article
- Functional characteristics of fresh antitumor immune interferer GDF-15 in multiple cancers.Scientific reports · 2025Article
- The Multifaceted Role of Growth Differentiation Factor 15 (GDF15): A Narrative Review from Cancer Cachexia to Target Therapy.Biomedicines · 2025Review
- Mechanical Loading of Osteocytes via Oscillatory Fluid Flow Regulates Early-Stage PC-3 Prostate Cancer Metastasis to Bone.Advanced biology · 2025Article
- Mapping growth differentiation factor-15 (GDF15)-mediated signaling pathways in cancer: insights into its role across different cancer types.Discover oncology · 2025Article
- Jujuboside B Inhibits the Proliferation and Migration of Non-Small Cell Lung Cancer H1299 Cells Through Inhibiting PI3K/Akt and Wnt/β-Catenin Pathways.Cancer management and research · 2025Article
- Identification of SETD4 as an Onco-Immunological Biomarker Encompassing the Tumor Microenvironment, Prognoses, and Therapeutic Responses in Various Human Cancers.Immunity, inflammation and disease · 2025Article
- Modelling bone metastasis in spheroids to study cancer progression and screen cisplatin efficacy.Cell proliferation · 2024Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Bone is the most frequent site of prostate cancer (PCa) metastasis; however, little is known about the role of the most common cell in bone, the osteocyte (OCy), in cancer biology. In this study we explored the crosstalk between PCa cells and OCys to determine if it contributes to PCa progression. PCa cells induced OCys to promote PCa proliferation, migration and invasion. A chemokine screen revealed that PCa cell induced OCys to produce growth-derived factor 15 (GDF15). Knockdown of GDF15 in OCys demonstrated that PCa cells conferred the ability on OCys to promote PCa proliferation, migration and invasion through GDF15. Consistent with this finding was the observation that the GDF15 receptor, GFRAL, was expressed on multiple PCa cell lines. Transcription factor array screening of PCa cells exposed to OCys with or without knockdown of GDF15 revealed that GDF15 in OCys promoted early growth response 1 (EGR1) expression in the PCa cells. Knockdown of EGR1 expression in PCa cells revealed it was required for the OCy-derived GDF15-mediated induction of in vitro PCa cell proliferation, migration and invasion. Subcutaneous co-injection of PCa cells and OCys into mice revealed that OCys promoted tumor growth in vivo, which was diminished by knockdown of GDF15 in the OCys. Knockdown of GDF15 in the tibiae diminished growth of PCa cancer cells injected into the tibiae, which was accompanied by decreased tumor cell proliferation and EGR1 expression. These results shed light on a novel mechanism through which PCa cells educate OCys to promote progression of PCa bone metastasis. They also suggest that targeting of GDF15-based and EGR1-based signaling pathways should be further explored for their potential to diminish progression of PCa bone metastasis.
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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.