ArticleJournal of cell science2012
PKD2 and PKD3 promote prostate cancer cell invasion by modulating NF-κB- and HDAC1-mediated expression and activation of uPA.
Article in Journal of cell science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- Advances in sequencing and omics studies in prostate cancer: unveiling molecular pathogenesis and clinical applications.Frontiers in oncology · 2024Pooled it
- Targeting PRKCN, an Essential Driver Orchestrating mTOR-IRF4 Axis Independently of Kinase Activity, in Multiple Myeloma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pan-cancer landscape of protein kinase D3: An integrative TCGA multi-omics analysis of clinical, molecular, and immunological roles.PloS one · 2026Article
- Golgi Drivers of Cancer.Sub-cellular biochemistry · 2026Review
- Protein kinase D2-mediated maintenance complex component 2 phosphorylation promotes bladder cancer progression.Journal of translational medicine · 2025Article
- A Protein Kinase Cε/Protein Kinase D3 Signalling Axis Modulates RhoA Activity During Cytokinesis.Biomedicines · 2025Article
- BRAT1 - a new therapeutic target for glioblastoma.Cellular and molecular life sciences : CMLS · 2025Article
- Transcriptome Analysis Suggests PKD3 Regulates Proliferative Glucose Metabolism, Calcium Homeostasis and Microtubule Dynamics After MEF Spontaneous Immortalization.International journal of molecular sciences · 2025Article
- Circadian rhythm disruption and endocrine-related tumors.World journal of clinical oncology · 2024Review
- Protein kinase D drives the secretion of invasion mediators in triple-negative breast cancer cell lines.iScience · 2024Article
- PRKD3 promotes proliferation of liver cancer cells: a downstream proteomics profiling study.American journal of translational research · 2024Article
- Rabeprazole suppressed gastric intestinal metaplasia through activation of GPX4-mediated ferroptosis.Frontiers in pharmacology · 2024Article
- Protein Kinase D2 and D3 Promote Prostate Cancer Cell Bone Metastasis by Positively Regulating Runx2 in a MEK/ERK1/2-Dependent Manner.The American journal of pathology · 2023Article
- Potential role for protein kinase D inhibitors in prostate cancer.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Protein Kinase D3 (PKD3) Requires Hsp90 for Stability and Promotion of Prostate Cancer Cell Migration.Cells · 2023Article
- Emerging photodynamic/sonodynamic therapies for urological cancers: progress and challenges.Journal of nanobiotechnology · 2022Review
- Review
- Golgi Complex: A Signaling Hub in Cancer.Cells · 2022Review
- Addressing the role of PKD3 in the T cell compartment with knockout mice.Cell communication and signaling : CCS · 2022Article
- Targeting Protein Kinases and Epigenetic Control as Combinatorial Therapy Options for Advanced Prostate Cancer Treatment.Pharmaceutics · 2022Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Although protein kinase D3 (PKD3) has been shown to contribute to prostate cancer cell growth and survival, the role of PKD in prostate cancer cell motility remains unclear. Here, we show that PKD2 and PKD3 promote nuclear factor kappa B (NF-κB) signaling and urokinase-type plasminogen activator (uPA) expression/activation, which are crucial for prostate cancer cell invasion. Silencing of endogenous PKD2 and/or PKD3 markedly decreased prostate cancer cell migration and invasion, reduced uPA and uPA receptor (uPAR) expression and increased plasminogen activator inhibitor-2 (PAI-2) expression. These results were further substantiated by the finding that PKD2 and PKD3 promoted the activity of uPA and matrix metalloproteinase 9 (MMP9). Furthermore, depletion of PKD2 and/or PKD3 decreased the level of binding of the p65 subunit of NF-κB to the promoter of the gene encoding uPA (PLAU), suppressing transcriptional activation of uPA. Endogenous PKD2 and PKD3 interacted with inhibitor of NF-κB (IκB) kinase β (IKKβ); PKD2 mainly regulated the phosphorylated IKK (pIKK)-phosphorylated IκB (pIκB)-IκB degradation cascade, p65 nuclear translocation, and phosphorylation of Ser276 on p65, whereas PKD3 was responsible for the phosphorylation of Ser536 on p65. Conversely, inhibition of uPA transactivation by PKD3 silencing was rescued by constitutive Ser536 p65 phosphorylation, and reduced tumor cell invasion resulting from PKD2 or PKD3 silencing was rescued by ectopic expression of p65. Interestingly, PKD3 interacted with histone deacetylase 1 (HDAC1), suppressing HDAC1 expression and decreasing its binding to the uPA promoter. Moreover, depletion of HDAC1 resulted in recovery of uPA transactivation in PKD3-knockdown cells. Taken together, these data suggest that PKD2 and PKD3 coordinate to promote prostate cancer cell invasion through p65 NF-κB- and HDAC1-mediated expression and activation of uPA.
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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.