ArticleOncogene2014
Protein kinase Cδ is required for ErbB2-driven mammary gland tumorigenesis and negatively correlates with prognosis in human breast cancer.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 53 citations in OpenAlex.
- Missense variants in PRKCD: elucidating their potential association with breast cancer.Breast cancer research : BCR · 2025Article
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- Inhibition of protein kinase C delta leads to cellular senescence to induce anti-tumor effects in colorectal cancer.Cancer science · 2023Article
- Proteomics separates adult-type diffuse high-grade gliomas in metabolic subgroups independent of 1p/19q codeletion and across IDH mutational status.Cell reports. Medicine · 2023Article
- Tumor PKCδ instigates immune exclusion in EGFR-mutated non-small cell lung cancer.BMC medicine · 2022Article
- The metabolomics of a protein kinase C delta (PKCδ) knock-out mouse model.Metabolomics : Official journal of the Metabolomic Society · 2022Article
- Protein Kinase C (PKC) Isozymes as Diagnostic and Prognostic Biomarkers and Therapeutic Targets for Cancer.Cancers · 2022Review
- Scalable multiplex co-fractionation/mass spectrometry platform for accelerated protein interactome discovery.Nature communications · 2022Article
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- Discovery of a signaling feedback circuit that defines interferon responses in myeloproliferative neoplasms.Nature communications · 2022Article
- Pharmacokinetic Assessment of Rottlerin fromACS omega · 2021Article
- L-plastin Ser5 phosphorylation is modulated by the PI3K/SGK pathway and promotes breast cancer cell invasiveness.Cell communication and signaling : CCS · 2021Article
- Co-administration of tyrosine kinase inhibitors with rottlerin in metastatic prostate cancer cells.EXCLI journal · 2021Article
- Equivocal, explicit and emergent actions of PKC isoforms in cancer.Nature reviews. Cancer · 2021Review
- Functional proteomic analysis reveals roles for PKCδ in regulation of cell survival and cell death: Implications for cancer pathogenesis and therapy.Advances in biological regulation · 2020Article
- Broad and thematic remodeling of the surfaceome and glycoproteome on isogenic cells transformed with driving proliferative oncogenes.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Src Kinase Is Biphosphorylated at Y416/Y527 and Activates the CUB-Domain Containing Protein 1/Protein Kinase C δ Pathway in a Subset of Triple-Negative Breast Cancers.The American journal of pathology · 2020Article
- EGF receptor and PKCδ kinase activate DNA damage-induced pro-survival and pro-apoptotic signaling via biphasic activation of ERK and MSK1 kinases.The Journal of biological chemistry · 2019Article
- Systemic analysis of tyrosine kinase signaling reveals a common adaptive response program in a HER2-positive breast cancer.Science signaling · 2019Article
- Improved synergistic anticancer efficacy of quercetin in combination with PI-103, rottlerin, and G0 6983 against MCF-7 and RAW 264.7 cells.In vitro cellular & developmental biology. Animal · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Protein kinase C δ (PKCδ) regulates apoptosis in the mammary gland, however, the functional contribution of PKCδ to the development or progression of breast cancer has yet to be determined. Meta-analysis of ErbB2-positive breast cancers shows increased PKCδ expression, and a negative correlation between PKCδ expression and prognosis. Here, we present in-vivo evidence that PKCδ is essential for the development of mammary gland tumors in a ErbB2-overexpressing transgenic mouse model, and in-vitro evidence that PKCδ is required for proliferative signaling downstream of the ErbB2 receptor. Mouse mammary tumor virus (MMTV)-ErbB2 mice lacking PKCδ (δKO) have increased tumor latency compared with MMTV-ErbB2 wild-type (δWT) mice, and the tumors show a dramatic decrease in Ki-67 staining. To explore the relationship between PKCδ and ErbB2-driven proliferation more directly, we used MCF-10A cells engineered to express a synthetic ligand-inducible form of the ErbB2 receptor. Depletion of PKCδ with short hairpin RNA inhibited ligand-induced growth in both two-dimensional (2D) (plastic) and three-dimensional (3D) (Matrigel) culture, and correlated with decreased phosphorylation of the ErbB2 receptor and reduced activation of Src and MAPK/ERK pathways. Similarly, in human breast cancer cell lines in which ErbB2 is overexpressed, depletion of PKCδ suppresses proliferation, Src and ERK activation. PKCδ appears to drive proliferation through the formation of an active ErbB2/PKCδ/Src signaling complex, as depletion of PKCδ disrupts association of Src with the ErbB2 receptor. Taken together, our studies present the first evidence that PKCδ is a critical regulator of ErbB2-mediated tumorigenesis, and suggest further investigation of PKCδ as a target in ErbB2-positive breast cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.