ArticleThe American journal of pathology2023
Protein Kinase D2 and D3 Promote Prostate Cancer Cell Bone Metastasis by Positively Regulating Runx2 in a MEK/ERK1/2-Dependent Manner.
Article in The American journal of pathology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- KIFC1 engages RUNX2/TGF-β signaling to promote lung cancer bone metastasis via disrupting bone homeostasis.Oncogene · 2026Article
- Mechanical activation of Piezo1 promotes osteoclastogenesis in orthodontic tooth movement.BMC oral health · 2026Article
- Targeting PRKCN, an Essential Driver Orchestrating mTOR-IRF4 Axis Independently of Kinase Activity, in Multiple Myeloma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- E2F1 K117 methylation by SETD6 disrupts BRD4-E2F1 binding and modulates E2F1 chromatin binding and gene regulation in prostate cancer cells.Nucleic acids research · 2026Article
- Protein kinase D2-mediated maintenance complex component 2 phosphorylation promotes bladder cancer progression.Journal of translational medicine · 2025Article
- Single-cell and bulk transcriptomics uncovers PRKD2-driven tumor stemness and progression in multiple myeloma.Scientific reports · 2025Article
- RUNX2 mediated epithelial mesenchymal transition induced by TGF beta and Smad signaling promotes malignant progression in glioma.Scientific reports · 2025Article
- Effect of PRKD3 on cell cycle in gastric cancer progression and downstream regulatory networks.Medical oncology (Northwood, London, England) · 2025Article
- Review
- Exosome encapsulation of miR-205-5p suppresses neuroblastoma progression by targeting RUNX2.World journal of pediatric surgery · 2025Article
- SLAMF8 regulates osteogenesis and adipogenesis of bone marrow mesenchymal stem cells via S100A6/Wnt/β-catenin signaling pathway.Stem cell research & therapy · 2024Article
- RUNX transcription factors: biological functions and implications in cancer.Clinical and experimental medicine · 2024Review
- Protein kinase D drives the secretion of invasion mediators in triple-negative breast cancer cell lines.iScience · 2024Article
- Protein kinase D1 - A targetable mediator of pancreatic cancer development.Biochimica et biophysica acta. Molecular cell research · 2024Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 3 countries.
Funding
Abstract
Advanced-stage prostate tumors metastasize to the bone, often causing death. The protein kinase D (PKD) family has been implicated in prostate cancer development; however, its role in prostate cancer metastasis remains elusive. This study examined the contribution of PKD, particularly PKD2 and PKD3 (PKD2/3), to the metastatic potential of prostate cancer cells and the effect of PKD inhibition on prostate cancer bone metastasis in vivo. Depletion of PKD2/3 by siRNAs or inhibition by the PKD inhibitor CRT0066101 in AR-positive and AR-negative castration-resistant prostate cancer cells potently inhibited colony formation and cell migration. Depletion or inhibition of PKD2/3 significantly blocked tumor cell invasion and suppressed the expression of genes related to bone metastasis in the highly invasive PC3-ML cells. The reduced invasive activity resulting from PKD2/3 depletion was in part mediated by the transcription factor Runx2, as its silencing decreased PKD2/3-mediated metastatic gene expression through the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase 1/2 signaling axis. Furthermore, inhibition of PKD by CRT0066101 potently decreased the frequency of bone micrometastases in a mouse model of bone metastasis based on intracardiac injection of PC3-ML cells. These results indicate that PKD2/3 plays an important role in the bone metastasis of prostate cancer cells, and its inhibition may be beneficial for the treatment of advanced prostate cancer.
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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 Socratic graph.