ArticleBreast cancer research : BCR2009
Protein kinase D1 regulates matrix metalloproteinase expression and inhibits breast cancer cell invasion.
Article in Breast cancer research : BCR, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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93 citing papers in PubMed, 147 citations in OpenAlex.
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- Integrative Machine Learning Model for Overall Survival Prediction in Breast Cancer Using Clinical and Transcriptomic Data.Biology · 2025Article
- A Case-Control Study on the Association BetweenHealth science reports · 2025Article
- Protein Kinase D1 (PRKD1) as a Diagnostic, Prognostic, and Immunomodulatory Biomarker in Human Cancers.Cureus · 2025Article
- Down-regulation of neuroprotective protein kinase D in Huntington´s disease.Cell death & disease · 2025Article
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- miR-410 Is a Key Regulator of Epithelial-to-Mesenchymal Transition with Biphasic Role in Prostate Cancer.Cancers · 2023Article
- Potential role for protein kinase D inhibitors in prostate cancer.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Membrane trafficking in breast cancer progression: protein kinase D comes into play.Frontiers in cell and developmental biology · 2023Review
- Bioactivity-guided fractionation ofFrontiers in cell and developmental biology · 2023Article
- The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update.Frontiers in immunology · 2023Review
- Golgi Complex: A Signaling Hub in Cancer.Cells · 2022Review
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- Cancer‑associated fibroblast‑derived LRRC15 promotes the migration and invasion of triple‑negative breast cancer cells via Wnt/β‑catenin signalling pathway regulation.Molecular medicine reports · 2022Article
- Camel Urine Promotes Sensitization to Doxorubicin by Inhibiting Epithelial-Mesenchymal Transition and Modulating NF-κB-Snail Signaling Pathway in Breast Cancer Cells.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Quercetin synergistically potentiates the anti-metastatic effect of 5-fluorouracil on the MDA-MB-231 breast cancer cell line.Iranian journal of basic medical sciences · 2021Article
- Review
- 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
- An Oxidative Stress-Related Gene Pair (Frontiers in immunology · 2021Article
33 more citing papers are in PubMed but not listed here.
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5 authors at 2 institutions in 1 country.
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Abstract
introductionThe biological and molecular events that regulate the invasiveness of breast tumour cells need to be further revealed to develop effective therapies that stop breast cancer from expanding and metastasising.
methodsHuman tissue samples of invasive breast cancer and normal breast, as well as breast cancer cell lines, were evaluated for protein kinase D (PKD) expression, to test if altered expression could serve as a marker for invasive breast cancer. We further utilised specific PKD1-shRNA and a system to inducibly-express PKD1 to analyse the role of PKD1 in the invasive behaviour of breast cancer cell lines in two-dimensional (2D) and three-dimensional (3D) culture. Invasive behaviour in breast cancer cell lines has been linked to matrix metalloproteinases (MMPs), so we also determined if PKD1 regulates the expression and activity of these enzymes.
resultsWe found that the serine/threonine kinase, PKD1, is highly expressed in ductal epithelial cells of normal human breast tissue, but is reduced in its expression in more than 95% of all analysed samples of human invasive breast tumours. Additionally, PKD1 is not expressed in highly invasive breast cancer cell lines, whereas non-invasive or very low-invasive breast cancer cell lines express PKD1. Our results further implicate that in MDA-MB-231 cells PKD1 expression is blocked by epigenetic silencing via DNA methylation. The re-expression of constitutively-active PKD1 in MDA-MB-231 cells drastically reduced their ability to invade in 2D and 3D cell culture. Moreover, MCF-7 cells acquired the ability to invade in 2D and 3D cell culture when PKD1 expression was knocked-down by shRNA. PKD1 also regulated the expression of breast cancer cell MMPs, MMP-2, MMP-7, MMP-9, MMP-10, MMP-11, MMP-13, MMP-14 and MMP-15, providing a potential mechanism for PKD1 mediation of the invasive phenotype.
conclusionsOur results identify decreased expression of the PKD1 as a marker for invasive breast cancer. They further suggest that the loss of PKD1 expression increases the malignant potential of breast cancer cells. This may be due to the function of PKD1 as a negative regulator of MMP expression. Our data suggest re-expression of PKD1 as a potential therapeutic strategy.
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