ArticleProceedings of the National Academy of Sciences of the United States of America2014
Tumor suppressor role of phospholipase C epsilon in Ras-triggered cancers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- An Association and Meta-Analysis of Esophageal Squamous Cell Carcinoma Risk Associated with PLCE1 rs2274223, C20orf54 rs13042395 and RUNX1 rs2014300 Polymorphisms.Pathology oncology research : POR · 2020Pooled it
- KRAS signaling networks, mutational heterogeneity, and emerging therapeutic strategies for cancer treatment.Biomarker research · 2026Review
- Increase of intracellular ZnScientific reports · 2025Article
- Integrative analysis of RAS signaling effectors reveals stage-dependent oncogenic patterns in colon adenocarcinoma.Biotechnology reports (Amsterdam, Netherlands) · 2025Article
- Multiple regulatory events contribute to a widespread circular RNA downregulation in precancer and early stage of colorectal cancer development.Biomarker research · 2025Article
- PLCγ2 controls neutrophil-like cell sensitivity through calcium oscillation and gates chemoattractant concentration range for chemotaxis.Frontiers in immunology · 2025Article
- Functional and structural insights into RAS effector proteins.Molecular cell · 2024Review
- Phospholipase Family Enzymes in Lung Cancer: Looking for Novel Therapeutic Approaches.Cancers · 2023Review
- Review
- Inhibition of the Phospholipase Cε-c-Jun N-Terminal Kinase Axis Suppresses Glioma Stem Cell Properties.International journal of molecular sciences · 2022Article
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- Dissecting the Mechanism of Action of Spiperone-A Candidate for Drug Repurposing for Colorectal Cancer.Cancers · 2022Article
- A novel NF-κB regulator encoded by circPLCE1 inhibits colorectal carcinoma progression by promoting RPS3 ubiquitin-dependent degradation.Molecular cancer · 2021Article
- Fluorogenic XY-69 in Lipid Vesicles for Measuring Activity of Phospholipase C Isozymes.Methods in molecular biology (Clifton, N.J.) · 2021Article
- The effects of mutant Ras proteins on the cell signalome.Cancer metastasis reviews · 2020Review
- A High-Throughput Assay to Identify Allosteric Inhibitors of the PLC-γ Isozymes Operating at Membranes.Biochemistry · 2020Article
- Phosphoinositide-Dependent Signaling in Cancer: A Focus on Phospholipase C Isozymes.International journal of molecular sciences · 2020Review
- PLCε knockdown prevents serine/glycine metabolism and proliferation of prostate cancer by suppressing YAP.American journal of cancer research · 2020Article
- A membrane-associated, fluorogenic reporter for mammalian phospholipase C isozymes.The Journal of biological chemistry · 2018Article
- The Role of Phospholipase C Signaling in Macrophage-Mediated Inflammatory Response.Journal of immunology research · 2018Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Phospholipase Cε (PLCε) has been characterized as a direct effector of Ras in vitro and in cellular systems; however, the role of PLCε in tumorigenesis and its link to Ras in this context remain unclear. To assess the role of PLCε in Ras-driven cancers, we generated two new mouse strains: one carrying a targeted deletion of Plce (Plce(-/-)) and the other carrying mutant alleles of Plce unable to bind to Ras (Plce(RAm/RAm)). The Plce(-/-) and, to a lesser degree, Plce(RAm/RAm) transgenic mice exhibited increased susceptibility to tumor formation in the two-stage skin carcinogenesis protocol, revealing a tumor suppressor function for this PLC. This result also suggests that in this context Ras binding in part regulates functions of PLCε. Although significant differences were not seen in the LSL-Kras(G12D) nonsmall cell lung carcinoma model, down-regulation of PLCε was found in animal tumors and in cellular systems following expression of the oncogenic Ras. An inhibitory impact of PLCε on cell growth requires intact lipase activity and is likely mediated by protein kinase C enzymes. Further cellular studies suggest involvement of histone deacetylase in the mechanism of PLCε down-regulation. Taken together, our results show a previously unidentified tumor suppressor role for this PLC in animal models and, together with observations of marked down-regulation in colorectal, lung, and skin tumors, suggest its use as a biological marker in 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.