ArticleCell communication and signaling : CCS2021
The phospholipase D inhibitor FIPI potently blocks EGF-induced calcium signaling in human breast cancer cells.
Article in Cell communication and signaling : CCS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 15 citations in OpenAlex.
- Ginsenoside Compound K Differentially Regulates Neuronal and Astrocytic CaPharmaceuticals (Basel, Switzerland) · 2026Article
- Phospholipase D: emerging therapeutic targets in signaling, metabolism, and immune-oncology.Cell communication and signaling : CCS · 2025Review
- The role of phosphatidylcholine metabolism in tumors.Medical oncology (Northwood, London, England) · 2025Review
- Choline-An Essential Nutrient with Health Benefits and a Signaling Molecule.International journal of molecular sciences · 2025Review
- PRL2 negatively regulates FcεRI mediated activation of mast cells.Cell death & disease · 2025Article
- Phosphatidic acid produced by phospholipase Dα1 and Dδ is incorporated into the internal membranes but not involved in the gene expression ofFrontiers in plant science · 2024Article
- Mitochondria-associated endoplasmic reticulum membrane: Overview and inextricable link with cancer.Journal of cellular and molecular medicine · 2023Review
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6 authors at 2 institutions in 1 country.
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Abstract
backgroundPhosphotyrosine kinase (PTK)-mediated phospholipase C-γ1 (PLC-γ1) signaling plays a crucial role in the release of the universal second messenger calcium from intracellular stores, which is mandatory for several cellular processes, including cell migration. However, PLC-γ1 could also be activated in a PTK-independent manner by phospholipase D (PLD)-derived phosphatidic acid (PA). Because both higher PLD expression levels and PLD activity have also been associated with breast cancer cell invasion and migration, we wondered whether there might be a link between PLD and PLC-γ1, which was investigated in this study. MATERIALS: MDA-MB-468-NEO (EGFR positive) and MDA-MB-468-HER2 (EGFR and HER2 positive) human breast cancer cells were used in this study. The migratory behavior of the cells in the presence of epidermal growth factor (EGF) and the PLD inhibitor 5-fluoro-2-indolyl-des-chlorohalopemide (FIPI) was analyzed using the 3D collagen matrix migration assay. Changes in cytosolic calcium levels in the presence of EGF, FIPI and Sig-1R agonists and antagonists as well as in PLD1 siRNA knockdown cells were determined by flow cytometry. Western blot analyses were performed to determine the basal expression levels and phosphorylation patterns of EGFR, HER2, AKT, MAPK
resultsThe EGF-induced migration of MDA-MB-468-NEO and MDA-MB-468-HER2 cells was significantly impaired by FIPI. Likewise, FIPI also significantly abolished EGF-induced calcium release in both cell lines. However, neither the expression levels nor the phosphorylation patterns of EGFR, HER2, AKT, MAPK
conclusionIn summary, blocking PLD activity with the specific inhibitor FIPI or knocking down PDL1 expression by siRNA significantly impaired EGF-induced calcium release in MDA-MB-468-NEO and MDA-MB-468-HER2 cells, likely indicating a connection between PLD activity and PLC-γ1-mediated calcium signaling. However, how PLD activity interferes with the release of calcium from intracellular stores remains unclear. Video Abstract.
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