ArticlePloS one2012
Protein kinase D1 maintains the epithelial phenotype by inducing a DNA-bound, inactive SNAI1 transcriptional repressor complex.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 50 citations in OpenAlex.
- Control of Snail1 protein stability by post-translational modifications: the basis for a complex regulation of Snail1 function.International journal of biological sciences · 2025Review
- Association between Single Nucleotide Polymorphisms ofFoods (Basel, Switzerland) · 2024Article
- The Post-Translational Regulation of Epithelial-Mesenchymal Transition-Inducing Transcription Factors in Cancer Metastasis.International journal of molecular sciences · 2021Review
- 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
- Regulation of Osteoclast Differentiation at Multiple Stages by Protein Kinase D Family Kinases.International journal of molecular sciences · 2020Article
- Ectopic expression of CNN2 of colon cancer promotes cell migration.Translational cancer research · 2020Article
- Twist1-Induced Epithelial Dissemination Requires Prkd1 Signaling.Cancer research · 2020Article
- Snail1: A Transcriptional Factor Controlled at Multiple Levels.Journal of clinical medicine · 2019Review
- High PKD2 predicts poor prognosis in lung adenocarcinoma via promoting Epithelial-mesenchymal Transition.Scientific reports · 2019Article
- Roles of the Phosphorylation of Transcriptional Factors in Epithelial-Mesenchymal Transition.Journal of oncology · 2019Review
- The phosphorylation status of PIP5K1C at serine 448 can be predictive for invasive ductal carcinoma of the breast.Oncotarget · 2018Article
- Protein kinase D inhibitor CRT0066101 suppresses bladder cancer growth in vitro and xenografts via blockade of the cell cycle at G2/M.Cellular and molecular life sciences : CMLS · 2018Article
- Protein kinase D1 regulates subcellular localisation and metastatic function of metastasis-associated protein 1.British journal of cancer · 2018Article
- Protein kinase D1: gatekeeper of the epithelial phenotype and key regulator of cancer metastasis?British journal of cancer · 2018Article
- SPSB3 targets SNAIL for degradation in GSK-3β phosphorylation-dependent manner and regulates metastasis.Oncogene · 2018Article
- 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
- The regulation of snail: on the ubiquitin edge.Cancer cell & microenvironment · 2017Article
- Protein Kinase D1 regulates focal adhesion dynamics and cell adhesion through Phosphatidylinositol-4-phosphate 5-kinase type-l γ.Scientific reports · 2016Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundProtein kinase D1 is downregulated in its expression in invasive ductal carcinoma of the breast and in invasive breast cancer cells, but its functions in normal breast epithelial cells is largely unknown. The epithelial phenotype is maintained by cell-cell junctions formed by E-cadherin. In cancer cells loss of E-cadherin expression contributes to an invasive phenotype. This can be mediated by SNAI1, a transcriptional repressor for E-cadherin that contributes to epithelial-to-mesenchymal transition (EMT). METHODOLOGY/PRINCIPAL
findingsHere we show that PKD1 in normal murine mammary gland (NMuMG) epithelial cells is constitutively-active in its basal state and prevents a transition to a mesenchymal phenotype. Investigation of the involved mechanism suggested that PKD1 regulates the expression of E-cadherin at the promoter level through direct phosphorylation of the transcriptional repressor SNAI1. PKD1-mediated phosphorylation of SNAI1 occurs in the nucleus and generates a nuclear, inactive DNA/SNAI1 complex that shows decreased interaction with its co-repressor Ajuba. Analysis of human tissue samples with a newly-generated phosphospecific antibody for PKD1-phosphorylated SNAI1 showed that regulation of SNAI1 through PKD1 occurs in vivo in normal breast ductal tissue and is decreased or lost in invasive ductal carcinoma. CONCLUSIONS/SIGNIFICANCE: Our data describe a mechanism of how PKD1 maintains the breast epithelial phenotype. Moreover, they suggest, that the analysis of breast tissue for PKD-mediated phosphorylation of SNAI1 using our novel phosphoS11-SNAI1-specific antibody may allow predicting the invasive potential of breast cancer cells.
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