ArticleScientific reports2019
Differential Regulation of Gene Expression in Lung Cancer Cells by Diacyglycerol-Lactones and a Phorbol Ester Via Selective Activation of Protein Kinase C Isozymes.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Positive selection screen identifies natural product β-catenin inactivators.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeted lipidomics between hPheo1 and SDHB KD cells reveal changes in bioactive lipids and PKC with polyamine pathway inhibition.Physiological reports · 2026Article
- Depth-corrected multi-factor dissection of chromatin accessibility for scATAC-seq data with PACS.Nature communications · 2025Article
- Synthesis and evaluation of DAG-lactone derivatives with HIV-1 latency reversing activity.European journal of medicinal chemistry · 2023Article
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- The Landscape of Lipid Metabolism in Lung Cancer: The Role of Structural Profiling.Journal of clinical medicine · 2023Article
- Radiosensitivity in Non-Small-Cell Lung Cancer by MMP10 through the DNA Damage Repair Pathway.Journal of oncology · 2023Article
- PROTEIN KINASE C ALPHA IS A CENTRAL NODE FOR TUMORIGENIC TRANSCRIPTIONAL NETWORKS IN HUMAN PROSTATE CANCER.Cancer research communications · 2022Article
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- FARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma.Cell reports · 2021Article
- Design, Synthesis, and Characterization of NovelJournal of medicinal chemistry · 2021Article
- The complexities of PKCα signaling in cancer.Advances in biological regulation · 2021Review
- Natural and Synthetic Lactones Possessing Antitumor Activities.International journal of molecular sciences · 2021Review
- Article
- Structural insights into C1-ligand interactions: Filling the gaps by in silico methods.Advances in biological regulation · 2021Review
- PKCCancer research · 2020Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Despite our extensive knowledge on the biology of protein kinase C (PKC) and its involvement in disease, limited success has been attained in the generation of PKC isozyme-specific modulators acting via the C1 domain, the binding site for the lipid second messenger diacylglycerol (DAG) and the phorbol ester tumor promoters. Synthetic efforts had recently led to the identification of AJH-836, a DAG-lactone with preferential affinity for novel isozymes (nPKCs) relative to classical PKCs (cPKCs). Here, we compared the ability of AJH-836 and a prototypical phorbol ester (phorbol 12-myristate 13-acetate, PMA) to induce changes in gene expression in a lung cancer model. Gene profiling analysis using RNA-Seq revealed that PMA caused major changes in gene expression, whereas AJH-836 only induced a small subset of genes, thus providing a strong indication for a major involvement of cPKCs in their control of gene expression. MMP1, MMP9, and MMP10 were among the genes most prominently induced by PMA, an effect impaired by RNAi silencing of PKCα, but not PKCδ or PKCε. Comprehensive gene signature analysis and bioinformatics efforts, including functional enrichment and transcription factor binding site analyses of dysregulated genes, identified major differences in pathway activation and transcriptional networks between PMA and DAG-lactones. In addition to providing solid evidence for the differential involvement of individual PKC isozymes in the control of gene expression, our studies emphasize the importance of generating targeted C1 domain ligands capable of differentially regulating PKC isozyme-specific function in cellular models.
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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 Socratic graph.