ArticleScience signaling2012
Key roles for the lipid signaling enzyme phospholipase d1 in the tumor microenvironment during tumor angiogenesis and metastasis.
Article in Science signaling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
77 citing papers in PubMed, 133 citations in OpenAlex.
- Development and Evaluation of Indole-Based Phospholipase D Inhibitors for Lung Cancer Immunotherapy.Journal of medicinal chemistry · 2025Article
- Inhibition of phospholipase D1 reduces pancreatic carcinogenesis in mice partly through a FAK-dependent mechanism.Carcinogenesis · 2025Article
- Phospholipase D1 is a critical mediator of neutrophil extracellular trap formation and venous thrombosis.Frontiers in immunology · 2025Article
- Effects of phospholipase D1-inhibitory peptide on the growth and metastasis of gastric cancer cells.Molecules and cells · 2024Article
- Liposomal Nano-Based Drug Delivery Systems for Breast Cancer Therapy: Recent Advances and Progresses.Anti-cancer agents in medicinal chemistry · 2024Review
- Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics.Journal of hematology & oncology · 2023Review
- Phospholipase Family Enzymes in Lung Cancer: Looking for Novel Therapeutic Approaches.Cancers · 2023Review
- A mass spectrometry imaging and lipidomic investigation reveals aberrant lipid metabolism in the orthotopic mouse glioma.Journal of lipid research · 2022Article
- Exosome Secretion and Epithelial-Mesenchymal Transition in Ovarian Cancer Are Regulated by Phospholipase D.International journal of molecular sciences · 2022Article
- Inhibition of phospholipase D1 induces immunogenic cell death and potentiates cancer immunotherapy in colorectal cancer.Experimental & molecular medicine · 2022Article
- Phosphatidylcholine-Derived Lipid Mediators: The Crosstalk Between Cancer Cells and Immune Cells.Frontiers in immunology · 2022Review
- Co-Targeting Tumor Angiogenesis and Immunosuppressive Tumor Microenvironment: A Perspective in Ethnopharmacology.Frontiers in pharmacology · 2022Review
- Hypoxia-induced cofilin 1 promotes hepatocellular carcinoma progression by regulating the PLD1/AKT pathway.Clinical and translational medicine · 2021Article
- Understanding the role of integrins in breast cancer invasion, metastasis, angiogenesis, and drug resistance.Oncogene · 2021Review
- Structure and regulation of human phospholipase D.Advances in biological regulation · 2021Review
- Aldolase A and Phospholipase D1 Synergistically Resist Alkylating Agents and Radiation in Lung Cancer.Frontiers in oncology · 2021Article
- Phospholipase Signaling in Breast Cancer.Advances in experimental medicine and biology · 2021Review
- D-series Resolvins activate Phospholipase D in phagocytes during inflammation and resolution.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Phospholipase D1 inhibition sensitizes glioblastoma to temozolomide and suppresses its tumorigenicity.The Journal of pathology · 2020Article
- Increased phospholipase D activity contributes to tumorigenesis in prostate cancer cell models.Molecular and cellular biochemistry · 2020Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Angiogenesis inhibitors, which target tumor cells, confer only short-term benefits on tumor growth. We report that ablation of the lipid signaling enzyme phospholipase D1 (PLD1) in the tumor environment compromised the neovascularization and growth of tumors. PLD1 deficiency suppressed the activation of Akt and mitogen-activated protein kinase signaling pathways by vascular endothelial growth factor in vascular endothelial cells, resulting in decreased integrin-dependent cell adhesion to, and migration on, extracellular matrices, as well as reduced tumor angiogenesis in a xenograft model. In addition, mice lacking PLD1 incurred fewer lung metastases than did wild-type mice. Bone marrow transplantation and binding studies identified a platelet-derived mechanism involving decreased tumor cell-platelet interactions, in part because of impaired activation of αIIbβ3 integrin in platelets, which decreased the seeding of tumor cells into the lung parenchyma. Treatment with a small-molecule inhibitor of PLD1 phenocopied PLD1 deficiency, efficiently suppressing both tumor growth and metastasis in mice. These findings reveal that PLD1 in the tumor environment promotes tumor growth and metastasis and, taken together with previous reports on the roles of PLD in tumor cell-intrinsic adaptations to stress, suggest the potential use of PLD inhibitors as cancer therapeutics.
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Registered trials
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.