ArticleOncotarget2015
The LPA1/ZEB1/miR-21-activation pathway regulates metastasis in basal breast cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 64 citations in OpenAlex.
- LPA1-Induced EMT of Retinal Pigment Epithelial Cells Promotes Subretinal Fibrosis via USP1-Mediated Deubiquitination and Stabilization of ZEB1.Investigative ophthalmology & visual science · 2026Article
- Epigenetic alterations in cancer metastasis: molecular mechanisms and implications for precision oncology.Frontiers in oncology · 2026Review
- The Use of Biologics for Targeting GPCRs in Metastatic Cancers.Biotech (Basel (Switzerland)) · 2025Review
- Dual-regulatory miRNAs: master regulators and therapeutic targets in bone-metastatic breast cancer.Frontiers in molecular biosciences · 2025Review
- Review
- Unveiling the therapeutic promise: exploring Lysophosphatidic Acid (LPA) signaling in malignant bone tumors for novel cancer treatments.Lipids in health and disease · 2024Review
- 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
- Lysophosphatidic Acid Induces Podocyte Pyroptosis in Diabetic Nephropathy by an Increase of Egr1 Expression via Downregulation of EzH2.International journal of molecular sciences · 2023Article
- Bone Metastases and Health in Prostate Cancer: From Pathophysiology to Clinical Implications.Cancers · 2023Review
- A reciprocal feedback between colon cancer cells and Schwann cells promotes the proliferation and metastasis of colon cancer.Journal of experimental & clinical cancer research : CR · 2022Article
- Designing Dual Inhibitors of Autotaxin-LPAR GPCR Axis.Molecules (Basel, Switzerland) · 2022Review
- Article
- Influence of the autotaxin-lysophosphatidic acid axis on cellular function and cytokine expression in different breast cancer cell lines.Scientific reports · 2022Article
- Lysophosphatidic Acid Signaling and microRNAs: New Roles in Various Cancers.Frontiers in oncology · 2022Review
- Neural Crest-Like Stem Cell Transcriptome Analysis Identifies LPAR1 in Melanoma Progression and Therapy Resistance.Cancer research · 2021Article
- Transcriptomics and Metabolomics Integration Reveals Redox-Dependent Metabolic Rewiring in Breast Cancer Cells.Cancers · 2021Article
- Review
- MicroRNAs and Their Roles in Breast Cancer Bone Metastasis.Current osteoporosis reports · 2021Review
- A Forgotten Corner in Cancer Immunotherapy: The Role of Lipids.Frontiers in oncology · 2021Review
- Identified the novel resistant biomarkers for taxane-based therapy for triple-negative breast cancer.International journal of medical sciences · 2021Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Lysophosphatidic acid (LPA) is a bioactive lipid promoting cancer metastasis. LPA activates a series of six G protein-coupled receptors (LPA1-6). While blockage of LPA1in vivo inhibits breast carcinoma metastasis, down-stream genes mediating LPA-induced metastasis have not been yet identified. Herein we showed by analyzing publicly available expression data from 1488 human primary breast tumors that the gene encoding the transcription factor ZEB1 was the most correlated with LPAR1 encoding LPA1. This correlation was most prominent in basal primary breast carcinomas and restricted to cell lines of basal subtypes. Functional experiments in three different basal cell lines revealed that LPA-induced ZEB1 expression was regulated by the LPA1/Phosphatidylinositol-3-Kinase (Pi3K) axis. DNA microarray and real-time PCR analyses further demonstrated that LPA up-regulated the oncomiR miR-21 through an LPA1/Pi3K/ZEB1-dependent mechanism. Strikingly, treatment with a mirVana miR-21 inhibitor, or silencing LPA1 or ZEB1 completely blocked LPA-induced cell migration in vitro, invasion and tumor cell bone colonization in vivo, which can be restored with a mirVana miR-21 mimic. Finally, high LPAR1 expression in basal breast tumors predicted worse lung-metastasis-free survival. Collectively, our results elucidate a new molecular pathway driving LPA-induced metastasis, thus underscoring the therapeutic potential of targeting LPA1 in patients with basal breast carcinomas.
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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.