ArticleMolecular biology of the cell2014
Protein kinase D2 induces invasion of pancreatic cancer cells by regulating matrix metalloproteinases.
Article in Molecular biology of the cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 58 citations in OpenAlex.
- Golgi Retention and Oncogenic Signaling of KIT Tyrosine Kinase in Gastrointestinal Stromal Tumor.Sub-cellular biochemistry · 2026Review
- 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
- The crosstalk between non-coding RNAs and oxidative stress in cancer progression.Genes & diseases · 2025Review
- 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
- Combination therapy of doxorubicin and Sildenafil inhibits the growth of pediatric rhabdomyosarcoma.Journal of cancer research and clinical oncology · 2023Article
- Endothelial Protein kinase D1 is a major regulator of post-traumatic hyperinflammation.Frontiers in immunology · 2023Article
- Golgi Complex: A Signaling Hub in Cancer.Cells · 2022Review
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- Multifaceted Functions of Protein Kinase D in Pathological Processes and Human Diseases.Biomolecules · 2021Review
- Sildenafil triggers tumor lethality through altered expression of HSP90 and degradation of PKD2.Carcinogenesis · 2020Article
- Elevated matrix metalloproteinase 7 expression promotes the proliferation, motility and metastasis of tongue squamous cell carcinoma.BMC cancer · 2020Article
- Physical plasma-triggered ROS induces tumor cell death upon cleavage of HSP90 chaperone.Scientific reports · 2019Article
- The phosphorylation status of PIP5K1C at serine 448 can be predictive for invasive ductal carcinoma of the breast.Oncotarget · 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
- Src-mediated tyrosine phosphorylation of Protein Kinase D2 at focal adhesions regulates cell adhesion.Scientific reports · 2017Article
- Protein kinase D signaling in cancer: A friend or foe?Biochimica et biophysica acta. Reviews on cancer · 2017Review
- Discovery of a potent protein kinase D inhibitor: insights in the binding mode of pyrazolo[3,4-MedChemComm · 2017Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic cancer cell invasion, metastasis, and angiogenesis are major challenges for the development of novel therapeutic strategies. Protein kinase D (PKD) isoforms are involved in controlling tumor cell motility, angiogenesis, and metastasis. In particular PKD2 expression is up-regulated in pancreatic cancer, whereas PKD1 expression is lowered. We report that both kinases control pancreatic cancer cell invasive properties in an isoform-specific manner. PKD2 enhances invasion in three-dimensional extracellular matrix (3D-ECM) cultures by stimulating expression and secretion of matrix metalloproteinases 7 and 9 (MMP7/9), by which MMP7 is likely to act upstream of MMP9. Knockdown of MMP7/9 blocks PKD2-mediated invasion in 3D-ECM assays and in vivo using tumors growing on chorioallantois membranes. Furthermore, MMP9 enhances PKD2-mediated tumor angiogenesis by releasing extracellular matrix-bound vascular endothelial growth factor A, increasing its bioavailability and angiogenesis. Of interest, specific knockdown of PKD1 in PKD2-expressing pancreatic cancer cells further enhanced the invasive properties in 3D-ECM systems by generating a high-motility phenotype. Loss of PKD1 thus may be beneficial for tumor cells to enhance their matrix-invading abilities. In conclusion, we define for the first time PKD1 and 2 isoform-selective effects on pancreatic cancer cell invasion and angiogenesis, in vitro and in vivo, addressing PKD isoform specificity as a major factor for future therapeutic strategies.
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