ArticleCarcinogenesis2011
A protein kinase C/protein kinase D pathway protects LNCaP prostate cancer cells from phorbol ester-induced apoptosis by promoting ERK1/2 and NF-{kappa}B activities.
Article in Carcinogenesis, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- Potential role for protein kinase D inhibitors in prostate cancer.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Bioactive Compounds and Their Impact on Protein Modification in Human Cells.International journal of molecular sciences · 2022Article
- Golgi Complex: A Signaling Hub in Cancer.Cells · 2022Review
- Targeting Protein Kinases and Epigenetic Control as Combinatorial Therapy Options for Advanced Prostate Cancer Treatment.Pharmaceutics · 2022Review
- Multifaceted Functions of Protein Kinase D in Pathological Processes and Human Diseases.Biomolecules · 2021Review
- Small-Molecule Inhibitor Targeting Protein Kinase D: A Potential Therapeutic Strategy.Frontiers in oncology · 2021Review
- High PKD2 predicts poor prognosis in lung adenocarcinoma via promoting Epithelial-mesenchymal Transition.Scientific reports · 2019Article
- Protein kinase D2: a versatile player in cancer biology.Oncogene · 2018Review
- Protein kinase D signaling in cancer: A friend or foe?Biochimica et biophysica acta. Reviews on cancer · 2017Review
- Type Iγ phosphatidylinositol phosphate kinase regulates PD-L1 expression by activating NF-κB.Oncotarget · 2017Article
- Androgen suppresses protein kinase D1 expression through fibroblast growth factor receptor substrate 2 in prostate cancer cells.Oncotarget · 2017Article
- Protein Kinase D: A Potential Therapeutic Target in Prostate Cancer.Molecular and cellular pharmacology · 2017Article
- Subtilase cytotoxin produced by locus of enterocyte effacement-negative Shiga-toxigenic Escherichia coli induces stress granule formation.Cellular microbiology · 2016Article
- Investigation the mechanism of the apoptosis induced by lactacystin in gastric cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- The natural compound Guttiferone F sensitizes prostate cancer to starvation induced apoptosis via calcium and JNK elevation.BMC cancer · 2015Article
- Effects of valproate sodium on extracellular signal-regulated kinase 1/2 phosphorylation following hippocampal neuronal epileptiform discharge in rats.Experimental and therapeutic medicine · 2013Article
- In vitro cytotoxicity, pharmacokinetics, tissue distribution, and metabolism of small-molecule protein kinase D inhibitors, kb-NB142-70 and kb-NB165-09, in mice bearing human cancer xenografts.Cancer chemotherapy and pharmacology · 2013Article
- Dissecting Major Signaling Pathways throughout the Development of Prostate Cancer.Prostate cancer · 2013Article
- Phorbol esters from Jatropha meal triggered apoptosis, activated PKC-δ, caspase-3 proteins and down-regulated the proto-oncogenes in MCF-7 and HeLa cancer cell lines.Molecules (Basel, Switzerland) · 2012Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Phorbol esters such as phorbol 12-myristate 13-acetate (PMA) induce apoptosis in many tumor cells including the androgen-sensitive LNCaP prostate cancer cells. Although phorbol ester-induced apoptotic pathways have been well characterized, little is known of the pro-survival pathways modulated by these agents. We now provide experimental evidence to indicate that protein kinase D (PKD) promotes survival signals in LNCaP cells in response to PMA treatment. Knockdown of endogenous PKD1 or PKD2 decreased extracellular signal-regulated kinase (ERK) 1/2 and nuclear factor-kappaB (NF-κB)-dependent transcriptional activities and potentiated PMA-induced apoptosis, whereas overexpression of wild-type PKD1 enhanced ERK1/2 activity and suppressed PMA-induced apoptosis. PMA caused rapid activation, followed by progressive downregulation of endogenous PKD1 in a time- and concentration-dependent manner. The downregulation of PKD1 was dependent on the activity of protein kinase C (PKC), but not that of PKD. Selective depletion of endogenous PKC isoforms revealed that both PKCδ and PKCε were required for PKD1 activation and subsequent downregulation. Further analysis showed that the downregulation of PKD1 was mediated by a ubiquitin-proteasome degradation pathway, inhibition of which correlated to increased cell survival. In summary, our data indicate that PKD1 is activated and downregulated by PMA through a PKC-dependent ubiquitin-proteasome degradation pathway, and the activation of PKD1 or PKD2 counteracts PMA-induced apoptosis by promoting downstream ERK1/2 and NF-κB activities in LNCaP prostate cancer cells.
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