ArticleOncogene2018
LPA signaling is regulated through the primary cilium: a novel target in glioblastoma.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic Review of Molecular Targeted Therapies for Adult-Type Diffuse Glioma: An Analysis of Clinical and Laboratory Studies.International journal of molecular sciences · 2023Pooled it
- The primary cilium at the helm: gatekeeper of TGF-β superfamily signaling in development, homeostasis, and disease.Biochemical Society transactions · 2026Review
- The DNA-PKcs-primary cilia axis maintains ionizing radiation-induced senescence in tumor cells.Acta biochimica et biophysica Sinica · 2025Article
- Unveiling the potential of biomechanics in pioneering innovative strategies for cancer therapy.Theranostics · 2025Review
- Molecular Targeted Therapies in Glioblastoma Multiforme: A Systematic Overview of Global Trends and Findings.Brain sciences · 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
- Establishment and Comprehensive Molecular Characterization of an Immortalized Glioblastoma Cell Line from a Brazilian Patient.International journal of molecular sciences · 2023Article
- Regulation of CD8 T-cell signaling, metabolism, and cytotoxic activity by extracellular lysophosphatidic acid.Immunological reviews · 2023Review
- Review
- Development of DNA aptamers for visualization of glial brain tumors and detection of circulating tumor cells.Molecular therapy. Nucleic acids · 2023Article
- Review
- Primary cilia: a novel research approach to overcome anticancer drug resistance.Frontiers in molecular biosciences · 2023Review
- Cilia at the Crossroads of Tumor Treating Fields and Chemotherapy.Developmental neuroscience · 2023Review
- Patterns of Ciliation and Ciliary Signaling in Cancer.Reviews of physiology, biochemistry and pharmacology · 2023Review
- TTBK2 controls cilium stability by regulating distinct modules of centrosomal proteins.Molecular biology of the cell · 2023Article
- Lipid Alterations in Glioma: A Systematic Review.Metabolites · 2022Review
- Design of Nanoparticles in Cancer Therapy Based on Tumor Microenvironment Properties.Pharmaceutics · 2022Review
- Primary cilia in the postnatal brain: Subcellular compartments for organizing neuromodulatory signaling.Current opinion in neurobiology · 2022Review
- Targeting lysophosphatidic acid receptor with Ki16425 impedes T cell lymphoma progression through apoptosis induction, glycolysis inhibition, and activation of antitumor immune response.Apoptosis : an international journal on programmed cell death · 2022Article
- Post-transcriptional and Post-translational Modifications of Primary Cilia: How to Fine Tune Your Neuronal Antenna.Frontiers in cellular neuroscience · 2022Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
The primary cilium is a ubiquitous organelle presented on most human cells. It is a crucial signaling hub for multiple pathways including growth factor and G-protein coupled receptors. Loss of primary cilia, observed in various cancers, has been shown to affect cell proliferation. Primary cilia formation is drastically decreased in glioblastoma (GBM), however, the role of cilia in normal astrocyte or glioblastoma proliferation has not been explored. Here, we report that loss of primary cilia in human astrocytes stimulates growth rate in a lysophosphatidic acid (LPA)-dependent manner. We show that lysophosphatidic acid receptor 1 (LPAR1) is accumulated in primary cilia. LPAR1 signaling through Gα12/Gαq was previously reported to be responsible for cancer cell proliferation. We found that in ciliated cells, Gα12 and Gαq are excluded from the cilium, creating a barrier against unlimited proliferation, one of the hallmarks of cancer. Upon loss of primary cilia, LPAR1 redistributes to the plasma membrane with a concomitant increase in LPAR1 association with Gα12 and Gαq. Inhibition of LPA signaling with the small molecule compound Ki16425 in deciliated highly proliferative astrocytes or glioblastoma patient-derived cells/xenografts drastically suppresses their growth both in vitro and in vivo. Moreover, Ki16425 brain delivery via PEG-PLGA nanoparticles inhibited tumor progression in an intracranial glioblastoma PDX model. Overall, our findings establish a novel mechanism by which primary cilium restricts proliferation and indicate that loss of primary cilia is sufficient to increase mitogenic signaling, and is important for the maintenance of a highly proliferative phenotype. Clinical application of LPA inhibitors may prove beneficial to restrict glioblastoma growth and ensure local control of disease.
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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.