ArticleMolecular cancer2019
Epigenetically upregulated oncoprotein PLCE1 drives esophageal carcinoma angiogenesis and proliferation via activating the PI-PLCε-NF-κB signaling pathway and VEGF-C/ Bcl-2 expression.
Article in Molecular cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 3 of them syntheses that pooled it.
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Who cites it
131 citing papers in PubMed, 3 syntheses or guidelines pooled it, 476 citations in OpenAlex.
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- The role of nutrition in harnessing the immune system: a potential approach to prevent cancer.Medical oncology (Northwood, London, England) · 2022Pooled it
- Circular RNAs in ferroptosis regulation and tumor progression of gynecological and breast cancers: molecular mechanisms and therapeutic potential.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Esophageal cancer: from pathogenesis to precision therapies.Signal transduction and targeted therapy · 2026Review
- The Role of Non-coding RNAs in Connective Tissue Diseases: Diagnostic and Therapeutic Potential of miRNAs, lncRNAs and circRNAs.Molecular diagnosis & therapy · 2026Review
- A20 Facilitates Oxaliplatin Sensitivity in Colorectal Cancer Through Monoubiquitylation of IKK-β.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cost-effective non-additive GWAS across 2329 diseases in 500,349 individuals.Nature communications · 2025Article
- Targeting inflammation-driven tumor progression with Zafirlukast via modulation of Jagged-1/Notch-1/Hes-1, Wnt-4/β-catenin, and VEGF signaling pathways in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Understanding the conformational dynamics of PI3Kα due to helical domain mutations: insights from Markov state model analysis.Molecular diversity · 2025Article
- Phospholipase C epsilon 1 as a therapeutic target in cardiovascular diseases.Journal of advanced research · 2025Review
- Hsa_circ_0109320 Serves as a Novel Circular RNA Biomarker in Non-small Cell Lung Cancer by Promoting Metastasis.Molecular biotechnology · 2025Article
- Epigenetically-Upregulated CD98 Shed Light on the Precancerous Diagnosis and Prognosis Prediction of Esophageal Cancer.Cancer science · 2025Article
- The polyphenolic compound, α-conidendrin, exerts anti-colon cancer and anti-angiogenic effects by targeting several signaling molecules.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Phospholipase Cε1 activates Rap1 signaling pathway to promote proliferation, EMT and angiogenesis of choriocarcinoma cells.Molecular biology reports · 2025Article
- Prediction of response to neoadjuvant chemotherapy in patients with muscle-invasive urothelial bladder cancer: role of immune-related gene expression.Cancer immunology, immunotherapy : CII · 2025Article
- Identifying the crucial oncogenic mechanisms of DDX56 based on a machine learning-based integration model of RNA-binding proteins.NPJ precision oncology · 2025Article
- Silencing lncRNA MCM3AP-AS1 protects against cisplatin-induced cell death in A549 lung cancer cells.Molecular biology reports · 2025Article
- Article
- Regulatory effects of lncRNA PVT1 on transcriptome in human breast cancer MDA-MB-231 cell line determined by in silico analyses.Chromosoma · 2025Article
71 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEsophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies. Neovascularization during tumorigenesis supplies oxygen and nutrients to proliferative tumor cells, and serves as a conduit for migration. Targeting oncogenes involved in angiogenesis is needed to treat organ-confined and locally advanced ESCC. Although the phospholipase C epsilon-1 (PLCE1) gene was originally identified as a susceptibility gene for ESCC, how PLCE1 is involved in ESCC is unclear.
methodsMatrix-assisted laser desorption ionization time-of-flight mass spectrometry were used to measure the methylation status of the PLCE1 promoter region. To validate the underlying mechanism for PLCE1 in constitutive activation of the NF-κB signaling pathway, we performed studies using in vitro and in vivo assays and samples from 368 formalin-fixed esophageal cancer tissues and 215 normal tissues with IHC using tissue microarrays and the Cancer Genome Atlas dataset.
resultsWe report that hypomethylation-associated up-regulation of PLCE1 expression was correlated with tumor angiogenesis and poor prognosis in ESCC cohorts. PLCE1 can activate NF-κB through phosphoinositide-phospholipase C-ε (PI-PLCε) signaling pathway. Furthermore, PLCE1 can bind p65 and IκBα proteins, promoting IκBα-S32 and p65-S536 phosphorylation. Consequently, phosphorylated IκBα promotes nuclear translocation of p50/p65 and p65, as a transcription factor, can bind vascular endothelial growth factor-C and bcl-2 promoters, enhancing angiogenesis and inhibiting apoptosis in vitro. Moreover, xenograft tumors in nude mice proved that PLCE1 can induce angiogenesis, inhibit apoptosis, and increase tumor aggressiveness via the NF-κB signaling pathway in vivo.
conclusionsOur findings not only provide evidence that hypomethylation-induced PLCE1 confers angiogenesis and proliferation in ESCC by activating PI-PLCε-NF-κB signaling pathway and VEGF-C/Bcl-2 expression, but also suggest that modulation of PLCE1 by epigenetic modification or a selective inhibitor may be a promising therapeutic approach for the treatment of ESCC.
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