ArticleScientific reports2015
Phosphatidic Acid (PA) can Displace PPARα/LXRα Binding to The EGFR Promoter Causing its Transrepression in Luminal Cancer Cells.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
- Evaluating rapid evaporative ionization mass spectrometry profiles of human breast cancer cells using a 3D in vitro assay.Analytical and bioanalytical chemistry · 2025Article
- Dysregulation of cellular membrane homeostasis as a crucial modulator of cancer risk.The FEBS journal · 2024Review
- Phosphatidic acid signaling and function in nuclei.Progress in lipid research · 2024Review
- Metabolic and immune-sensitive contacts between lipid droplets and endoplasmic reticulum reconstituted in vitro.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Gene by Environment Interactions reveal new regulatory aspects of signaling network plasticity.PLoS genetics · 2022Article
- shRNA-mediated PPARα knockdown in human glioma stem cells reduces in vitro proliferation and inhibits orthotopic xenograft tumour growth.The Journal of pathology · 2019Article
- Interaction and Regulation Between Lipid Mediator Phosphatidic Acid and Circadian Clock Regulators.The Plant cell · 2019Article
- Bioassay-guided isolation of cantharidin from blister beetles and its anticancer activity through inhibition of epidermal growth factor receptor-mediated STAT3 and Akt pathways.Journal of natural medicines · 2018Article
- How miRs and mRNA deadenylases could post-transcriptionally regulate expression of tumor-promoting protein PLD.Advances in biological regulation · 2018Review
- Dipalmitoylphosphatidic acid inhibits tumor growth in triple-negative breast cancer.International journal of biological sciences · 2017Article
- A Phosphatidic Acid (PA) conveyor system of continuous intracellular transport from cell membrane to nucleus maintains EGF receptor homeostasis.Oncotarget · 2016Article
- The transcription factors Slug (SNAI2) and Snail (SNAI1) regulate phospholipase D (PLD) promoter in opposite ways towards cancer cell invasion.Molecular oncology · 2016Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The expression of the epidermal growth factor receptor (EGFR) is highly regulated in normal cells, whereas some cancer cells have high constitutive levels. Understanding naturally-occurring ways of downregulating EGFR in cancer cells was investigated. Phosphatidic acid (PA) or Nuclear Receptors (NR) PPARα/RXRα/LXRα, enhance EGFR expression, mediated by the promoter region -856(A) to -226(T). Unexpectedly, the combination of NRs and PA caused repression. PA induces a conformational change in the nuclear receptor PPARα (increase of alpha-helices at the expense of decreasing beta-sheets), as evidenced by circular dichroism. This represses the naturally-enhancing capability of PPARα on EGFR transcription. PPARα-overexpressing cells in the presence of PA > 300 nM or the enzyme that produces it, phospholipase D (PLD), downregulate EGFR expression. The reasons are two-fold. First, PA displaces PPARα binding to the EGFR promoter at those concentrations. Second, NR heterodimer-dependent promoter activity is weakened in the presence of PA in vivo. Since other genes considered (β-catenin, cyclin D3, PLD2 and ACOX-1) are also downregulated with a PA + PPARα combination, the transrepression appears to be a global phenomenon. Lastly, the reported effect is greater in MCF-7 than in MDA-MB-231 breast cancer cells, which could provide a novel basis for regulating excessive expression of EGFR in luminal cancer cells.
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