ArticleMolecular cancer therapeutics2012
Inducible silencing of protein kinase D3 inhibits secretion of tumor-promoting factors in prostate cancer.
Article in Molecular cancer therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- The roles and mechanisms of SREBP1 in cancer development and drug response.Genes & diseases · 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
- 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
- Loss of Protein Kinase D2 Activity Protects Against Bleomycin-Induced Dermal Fibrosis in Mice.Laboratory investigation; a journal of technical methods and pathology · 2023Article
- Protein Kinase D3 (PKD3) Requires Hsp90 for Stability and Promotion of Prostate Cancer Cell Migration.Cells · 2023Article
- Membrane trafficking in breast cancer progression: protein kinase D comes into play.Frontiers in cell and developmental biology · 2023Review
- Addressing the role of PKD3 in the T cell compartment with knockout mice.Cell communication and signaling : CCS · 2022Article
- Multifaceted Functions of Protein Kinase D in Pathological Processes and Human Diseases.Biomolecules · 2021Review
- The oncogenic role of protein kinase D3 in cancer.Journal of Cancer · 2021Review
- Protein kinase Ds promote tumor angiogenesis through mast cell recruitment and expression of angiogenic factors in prostate cancer microenvironment.Journal of experimental & clinical cancer research : CR · 2019Article
- The phosphorylation status of PIP5K1C at serine 448 can be predictive for invasive ductal carcinoma of the breast.Oncotarget · 2018Article
- Analysis of oncogenic activities of protein kinase D1 in head and neck squamous cell carcinoma.BMC cancer · 2018Article
- Protein kinase D2: a versatile player in cancer biology.Oncogene · 2018Review
- Protein kinase D1: gatekeeper of the epithelial phenotype and key regulator of cancer metastasis?British journal of cancer · 2018Article
- Protein Kinase D Enzymes as Regulators of EMT and Cancer Cell Invasion.Journal of clinical medicine · 2016Review
- Opposing growth regulatory roles of protein kinase D isoforms in human keratinocytes.The Journal of biological chemistry · 2015Article
- Protein kinase d as a potential chemotherapeutic target for colorectal cancer.Molecular cancer therapeutics · 2014Article
- Elevated protein kinase D3 (PKD3) expression supports proliferation of triple-negative breast cancer cells and contributes to mTORC1-S6K1 pathway activation.The Journal of biological chemistry · 2014Article
- Protein kinase D2 induces invasion of pancreatic cancer cells by regulating matrix metalloproteinases.Molecular biology of the cell · 2014Article
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Authors and funding
5 authors.
Funding
Abstract
Protein kinase D (PKD) acts as a major mediator of several signaling pathways related to cancer development. Aberrant PKD expression and activity have been shown in multiple cancers, and novel PKD inhibitors show promising anticancer activities. Despite these advances, the mechanisms through which PKD contributes to the pathogenesis of cancer remain unknown. Here, we establish a novel role for PKD3, the least studied member of the PKD family, in the regulation of prostate cancer cell growth and motility through modulation of secreted tumor-promoting factors. Using both a stable inducible knockdown cell model and a transient knockdown system using multiple siRNAs, we show that silencing of endogenous PKD3 significantly reduces prostate cancer cell proliferation, migration, and invasion. In addition, conditioned medium from PKD3-knockdown cells exhibits less migratory potential compared with that from control cells. Further analysis indicated that depletion of PKD3 blocks secretion of multiple key tumor-promoting factors including matrix metalloproteinase (MMP)-9, interleukin (IL)-6, IL-8, and GROα but does not alter mRNA transcript levels for these factors, implying impairment of the secretory pathway. More significantly, inducible depletion of PKD3 in a subcutaneous xenograft model suppresses tumor growth and decreases levels of intratumoral GROα in mice. These data validate PKD3 as a promising therapeutic target in prostate cancer and shed light on the role of secreted tumor-promoting factors in prostate cancer progression.
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