ArticleHepatology (Baltimore, Md.)2019
The Chemosensory Function of Primary Cilia Regulates Cholangiocyte Migration, Invasion, and Tumor Growth.
Article in Hepatology (Baltimore, Md.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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
21 citing papers in PubMed, 45 citations in OpenAlex.
- Another ciliopathy? Uncovering the ciliary basis of biliary atresia.Hepatology international · 2026Review
- Primary Cilia in Hepatic Biliary Hyperplasia: Implications for Liver Diseases.Seminars in liver disease · 2025Review
- Cholangiocytes' primary cilia regulate DNA damage response and repair.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Review
- The Primary Cilia are Associated with the Axon Initial Segment in Neurons.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Neuronal guidance behaviours: the primary cilium perspective.Frontiers in cell and developmental biology · 2025Review
- Article
- METTL3-m6A methylation inhibits the proliferation and viability of type II alveolar epithelial cells in acute lung injury by enhancing the stability and translation efficiency of Pten mRNA.Respiratory research · 2024Article
- XIAP-mediated degradation of IFT88 disrupts HSC cilia to stimulate HSC activation and liver fibrosis.EMBO reports · 2024Article
- CXCL12 targets the primary cilium cAMP/cGMP ratio to regulate cell polarity during migration.Nature communications · 2023Article
- Review
- Primary Cilia Restrain PI3K-AKT Signaling to Orchestrate Human Decidualization.International journal of molecular sciences · 2022Article
- Clinical and genetic heterogeneity of primary ciliopathies (Review).International journal of molecular medicine · 2021Review
- Functional aspects of primary cilium in signaling, assembly and microenvironment in cancer.Journal of cellular physiology · 2021Review
- P2Y receptors for extracellular nucleotides: Contributions to cancer progression and therapeutic implications.Biochemical pharmacology · 2021Review
- Short-Chain Fatty Acid Butyrate Induces Cilia Formation and Potentiates the Effects of HDAC6 Inhibitors in Cholangiocarcinoma Cells.Frontiers in cell and developmental biology · 2021Article
- Identification of Key Functional Gene Signatures Indicative of Dedifferentiation in Papillary Thyroid Cancer.Frontiers in oncology · 2021Article
- The primary cilium: Its role as a tumor suppressor organelle.Biochemical pharmacology · 2020Review
- Review
- The Sensing Liver: Localization and Ligands for Hepatic Murine Olfactory and Taste Receptors.Frontiers in physiology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Cholangiocytes, the epithelial cells lining the biliary tree in the liver, express primary cilia that can detect several kinds of environmental signals and then transmit this information into the cell. We have reported that cilia are significantly reduced in cholangiocarcinoma (CCA) and that the experimental deciliation of normal cells induces a malignant-like phenotype with increased proliferation, anchorage-independent growth, invasion, and migration. Here, we tested the hypothesis that the chemosensory function of cholangiocyte primary cilia acts as a mechanism for tumor suppression. We found that in the presence of extracellular nucleotides cilia-dependent chemosensation of the nucleotides inhibited migration and invasion in normal ciliated cholangiocytes through a P2Y11 receptor and liver kinase B1 (LKB1)-phosphatase and tensin homolog-AKT-dependent mechanism. In contrast, in normal deciliated cholangiocytes and CCA cells, the nucleotides induced the opposite effects, i.e., increased migration and invasion. As activation of LKB1 through a cilia-dependent mechanism was required for the nucleotide-mediated inhibitory effects on migration and invasion, we attempted to activate LKB1 directly, independent of ciliary expression, using the compound hesperidin methyl chalcone (HMC). We found that HMC induced activation of LKB1 in both ciliated and deciliated cells in vitro, resulting in the inhibition of migration and proliferation. Furthermore, using a rat syngeneic orthotopic CCA model, we found that HMC inhibited tumor growth in vivo. Conclusion: These findings highlight the importance of the chemosensory function of primary cilia for the control of migration and invasion and suggest that, by directly activating LKB1 and bypassing the need for primary cilia, it is possible to emulate this chemosensory function in CCA cells; these data warrant further studies evaluating the possibility of using HMC as therapy for CCA.
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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 Socratic graph.