ArticleThe Journal of biological chemistry2009
Protein kinase Cdelta supports survival of MDA-MB-231 breast cancer cells by suppressing the ERK1/2 pathway.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
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- The C2 Domain of PKC‑δ as a Dominant-Negative Modulator of Breast Cancer Cell Survival and Chemosensitivity.ACS omega · 2025Article
- Comprehensive computational analysis of PKCδ non-synonymous variants identifies rs1703863535 as a potential breast cancer biomarker.BMC cancer · 2025Article
- Self-Assembled Molecular Complexes of 1,10-Phenanthroline and 2-Aminobenzimidazoles: Synthesis, Structure Investigations, and Cytotoxic Properties.Molecules (Basel, Switzerland) · 2024Article
- Insertion Depth Modulates Protein Kinase C-δ-C1b Domain Interactions with Membrane Cholesterol as Revealed by MD Simulations.International journal of molecular sciences · 2023Article
- Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer.International journal of molecular sciences · 2022Review
- The power of heteronemin in cancers.Journal of biomedical science · 2022Review
- PBLD inhibits angiogenesis via impeding VEGF/VEGFR2-mediated microenvironmental cross-talk between HCC cells and endothelial cells.Oncogene · 2022Article
- Effect of Estrogen on Heteronemin-Induced Anti-proliferative Effect in Breast Cancer Cells With Different Estrogen Receptor Status.Frontiers in cell and developmental biology · 2021Article
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- Nuclear-Biased DUSP6 Expression is Associated with Cancer Spreading Including Brain Metastasis in Triple-Negative Breast Cancer.International journal of molecular sciences · 2019Article
- Cytotoxic Activity of Royleanone Diterpenes fromACS omega · 2019Article
- Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability.International journal of molecular sciences · 2019Review
- BLT2, a leukotriene B4 receptor 2, as a novel prognostic biomarker of triple-negative breast cancer.BMB reports · 2018Review
- Molecular characterization of protein kinase C delta (PKCδ)-Smac interactions.BMC biochemistry · 2016Article
- Energy homeostasis genes and survival after breast cancer diagnosis: the Breast Cancer Health Disparities Study.Cancer causes & control : CCC · 2016Article
- Article
- Protein kinase Cδ is a therapeutic target in malignant melanoma with NRAS mutation.ACS chemical biology · 2014Article
- NEDD4: a promising target for cancer therapy.Current cancer drug targets · 2014Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mechanisms that mediate apoptosis resistance are attractive therapeutic targets for cancer. Protein kinase Cdelta (PKCdelta) is considered a pro-apoptotic factor in many cell types. In breast cancer, however, it has shown both pro-survival and pro-apoptotic effects. Here, we report for the first time that down-regulation of PKCdelta per se leads to apoptosis of MDA-MB-231 cells. Inhibition of MEK1/2 by either PD98059 or U0126 suppressed the induction of apoptosis of PKCdelta-depleted MDA-MB-231 cells but did not support survival of MCF-7 or MDA-MB-468 cells. Basal ERK1/2 phosphorylation was substantially higher in MDA-MB-231 cells than in the other cell lines. PKCdelta depletion led to even higher ERK1/2 phosphorylation levels and also to lower expression levels of the ERK1/2 phosphatase MKP3. Depletion of MKP3 led to apoptosis and higher levels of ERK1/2 phosphorylation, suggesting that this may be a mechanism mediating the effect of PKCdelta down-regulation. However, PKCdelta silencing also induced increased MEK1/2 phosphorylation, indicating that PKCdelta regulates ERK1/2 phosphorylation both upstream and downstream. Moreover, PKCdelta silencing led to increased levels of the E3 ubiquitin ligase Nedd4, which is a potential regulator of MKP3, because down-regulation led to increased MKP3 levels. Our results highlight PKCdelta as a potential target for therapy of breast cancers with high activity of the ERK1/2 pathway.
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