ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2020
HDAC6-dependent ciliophagy is involved in ciliary loss and cholangiocarcinoma growth in human cells and murine models.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 35 citations in OpenAlex.
- Primary cilia: sensors of biliary homeostasis and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Deciphering the tubulin code: roles and mechanisms of microtubule post-translational modifications in gastrointestinal tumors: a narrative review.Journal of gastrointestinal oncology · 2026Review
- Primary cilia in the hypothalamic AgRP neurons mediate metabolic effects of butyrate.Nature communications · 2026Article
- Primary cilia promote resistance to EGFR tyrosine kinase inhibitor, osimertinib, in non-small cell lung cancer.bioRxiv : the preprint server for biology · 2026Article
- Strategies for multimodal spatiotemporal profiling of phosphorylation in cilia biology.Journal of cell science · 2025Review
- Cholangiocytes' primary cilia regulate DNA damage response and repair.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Primary Cilia in Hepatic Biliary Hyperplasia: Implications for Liver Diseases.Seminars in liver disease · 2025Review
- Folliculin depletion results in liver cell damage and cholangiocarcinoma through MiT/TFE activation.Cell death and differentiation · 2025Article
- Histone Deacetylase 6 (HDAC6) in Ciliopathies: Emerging Insights and Therapeutic Implications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Unveiling the potential of biomechanics in pioneering innovative strategies for cancer therapy.Theranostics · 2025Review
- The exocyst complex and intracellular vesicles mediate soluble protein trafficking to the primary cilium.Communications biology · 2024Article
- Review
- Primary cilia: a novel research approach to overcome anticancer drug resistance.Frontiers in molecular biosciences · 2023Review
- Review
- Pathophysiology of Primary Cilia: Signaling and Proteostasis Regulation.Frontiers in cell and developmental biology · 2022Review
- Role of Selective Histone Deacetylase 6 Inhibitor ACY-1215 in Cancer and Other Human Diseases.Frontiers in pharmacology · 2022Review
- Tumor Treating Fields Suppression of Ciliogenesis Enhances Temozolomide Toxicity.Frontiers in oncology · 2022Article
- Article
- Functional aspects of primary cilium in signaling, assembly and microenvironment in cancer.Journal of cellular physiology · 2021Review
- HDAC6 Signaling at Primary Cilia Promotes Proliferation and Restricts Differentiation of Glioma Cells.Cancers · 2021Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Reduced ciliary expression is reported in several tumors, including cholangiocarcinoma (CCA). We previously showed primary cilia have tumor suppressor characteristics, and HDAC6 is involved in ciliary loss. However, mechanisms of ciliary disassembly are unknown. Herein, we tested the hypothesis that HDAC6-dependent autophagy of primary cilia, i.e., ciliophagy, is the main mechanism driving ciliary disassembly in CCA. Using the cancer genome atlas database, human CCA cells, and a rat orthotopic CCA model, we assessed basal and HDAC6-regulated autophagy levels. The effects of RNA-silencing or pharmacological manipulations of ciliophagy on ciliary expression were assessed. Interactions of ciliary proteins with autophagy machinery was assessed by immunoprecipitations. Cell proliferation was assessed by MTS and IncuCyte. A CCA rat model was used to assess the effects of pharmacological inhibition of ciliophagy in vivo. Autophagy is increased in human CCA, as well as in a rat orthotopic CCA model and human CCA cell lines. Autophagic flux was decreased via inhibition of HDAC6, while it was increased by its overexpression. Inhibition of autophagy and HDAC6 restores cilia and decreases cell proliferation. LC3 interacts with HDAC6 and ciliary proteins, and the autophagy cargo receptor involved in targeting ciliary components to the autophagy machinery is primarily NBR1. Treatment with chloroquine, Ricolinostat (ACY-1215), or their combination decreased tumor growth in vivo. Mice that overexpress the autophagy transcription factor TFEB show a decrease of ciliary number. These results suggest that ciliary disassembly is mediated by HDAC6-regulated autophagy, i.e., ciliophagy. Inhibition of ciliophagy may decrease cholangiocarcinoma growth and warrant further investigations as a potential therapeutic approach.
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