ArticleJournal of the National Cancer Institute2012
Effect of inhibition of the lysophosphatidic acid receptor 1 on metastasis and metastatic dormancy in breast cancer.
Article in Journal of the National Cancer Institute, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 152 citations in OpenAlex.
- Targeting dormant tumor cells to prevent recurrent breast cancer: a randomized phase 2 trial.Nature medicine · 2025Trial
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- Cancer treatments as paradoxical catalysts of tumor awakening in the lung.Cancer metastasis reviews · 2024Review
- Autophagy is required for mammary tumor recurrence by promoting dormant tumor cell survival following therapy.Breast cancer research : BCR · 2024Article
- Lysophosphatidic Acid Receptor 1 (LPAChemMedChem · 2024Article
- Autotaxin inhibition attenuates the aortic valve calcification by suppressing inflammation-driven fibro-calcific remodeling of valvular interstitial cells.BMC medicine · 2024Article
- A combined opposite targeting of p110δ PI3K and RhoA abrogates skin cancer.Communications biology · 2024Article
- A perspective on the metastasis suppressor field.Cancer metastasis reviews · 2023Review
- Integration of an LPAR1 Antagonist into Liposomes Enhances Their Internalization and Tumor Accumulation in an Animal Model of Human Metastatic Breast Cancer.Molecular pharmaceutics · 2023Article
- LPA1-mediated inhibition of CXCR4 attenuates CXCL12-induced signaling and cell migration.Cell communication and signaling : CCS · 2023Article
- Regulatory miRNAs in cancer cell recovery from therapy exposure and its implications as a novel therapeutic strategy for preventing disease recurrence.The Enzymes · 2023Article
- LINC00511/hsa-miR-573 axis-mediated high expression of Gasdermin C associates with dismal prognosis and tumor immune infiltration of breast cancer.Scientific reports · 2022Article
- Metabolomic Analysis of Plasma from Breast Cancer Patients Using Ultra-High-Performance Liquid Chromatography Coupled with Mass Spectrometry: An Untargeted Study.Metabolites · 2022Article
- Dormancy in Breast Cancer, the Role of Autophagy, lncRNAs, miRNAs and Exosomes.International journal of molecular sciences · 2022Review
- Article
- Clinical and Biological Aspects of Disseminated Tumor Cells and Dormancy in Breast Cancer.Frontiers in cell and developmental biology · 2022Review
- Autotaxin impedes anti-tumor immunity by suppressing chemotaxis and tumor infiltration of CD8Cell reports · 2021Article
- Neural Crest-Like Stem Cell Transcriptome Analysis Identifies LPAR1 in Melanoma Progression and Therapy Resistance.Cancer research · 2021Article
30 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundPrevious studies identified the human nonmetastatic gene 23 (NME1, hereafter Nm23-H1) as the first metastasis suppressor gene. An inverse relationship between Nm23-H1 and expression of lysophosphatidic acid receptor 1 gene (LPAR1, also known as EDG2 or hereafter LPA1) has also been reported. However, the effects of LPA1 inhibition on primary tumor size, metastasis, and metastatic dormancy have not been investigated.
methodsThe LPA1 inhibitor Debio-0719 or LPA1 short hairpinned RNA (shRNA) was used. Primary tumor size and metastasis were investigated using the 4T1 spontaneous metastasis mouse model and the MDA-MB-231T experimental metastasis mouse model (n = 13 mice per group). Proliferation and p38 intracellular signaling in tumors and cell lines were determined by immunohistochemistry and western blot to investigate the effects of LPA1 inhibition on metastatic dormancy. An analysis of variance-based two-tailed t test was used to determine a statistically significant difference between treatment groups.
resultsIn the 4T1 spontaneous metastasis mouse model, Debio-0719 inhibited the metastasis of 4T1 cells to the liver (mean = 25.2 liver metastases per histologic section for vehicle-treated mice vs 6.8 for Debio-0719-treated mice, 73.0% reduction, P < .001) and lungs (mean = 6.37 lesions per histologic section for vehicle-treated mice vs 0.73 for Debio-0719-treated mice, 88.5% reduction, P < .001), with no effect on primary tumor size. Similar results were observed using the MDA-MB-231T experimental pulmonary metastasis mouse model. LPA1 shRNA also inhibited metastasis but did not affect primary tumor size. In 4T1 metastases, but not primary tumors, expression of the proliferative markers Ki67 and pErk was reduced by Debio-0719, and phosphorylation of the p38 stress kinase was increased, indicative of metastatic dormancy.
conclusionThe data identify Debio-0719 as a drug candidate with metastasis suppressor activity, inducing dormancy at secondary tumor sites.
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