ArticleAmerican journal of respiratory cell and molecular biology2022
Screening for Inhibitors of YAP Nuclear Localization Identifies Aurora Kinase A as a Modulator of Lung Fibrosis.
Article in American journal of respiratory cell and molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- ADAMTS14 is a novel modulator of fibroblast mechanoactivation in pulmonary fibrosis.American journal of respiratory and critical care medicine · 2026Article
- Targeting YAP: mechanistic breakthroughs and therapeutic prospects in reversing organ fibrosis.Molecular and cellular biochemistry · 2026Review
- Review
- miR-301a-mediated crosstalk between the Hedgehog and HIPPO/YAP signaling pathways promotes pancreatic cancer.Cancer biology & therapy · 2025Article
- Mechanotransduction-Epigenetic Coupling in Pulmonary Regeneration: Multifunctional Bioscaffolds as Emerging Tools.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Computational Insights into the Polypharmacological Landscape of BCR-ABL Inhibitors: Emphasis on Imatinib and Nilotinib.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Identifying novel therapeutic targets in cystic fibrosis through advanced single-cell transcriptomics analysis.Computers in biology and medicine · 2025Article
- Multiscale computational model predicts how environmental changes and treatments affect microvascular remodeling in fibrotic disease.PNAS nexus · 2025Article
- Multiscale computational model predicts how environmental changes and drug treatments affect microvascular remodeling in fibrotic disease.bioRxiv : the preprint server for biology · 2024Article
- Divergent roles of the Hippo pathway in the pathogenesis of idiopathic pulmonary fibrosis: tissue homeostasis and fibrosis.Inflammation and regeneration · 2023Review
- A Glowing Opportunity to Target YAP in Lung Fibrosis.American journal of respiratory cell and molecular biology · 2022Article
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Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
Abstract
Idiopathic pulmonary fibrosis is a progressive lung disease with limited therapeutic options that is characterized by pathological fibroblast activation and aberrant lung remodeling with scar formation. YAP (Yes-associated protein) is a transcriptional coactivator that mediates mechanical and biochemical signals controlling fibroblast activation. We previously identified HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors (statins) as YAP inhibitors based on a high-throughput small-molecule screen in primary human lung fibroblasts. Here we report that several Aurora kinase inhibitors were also identified from the top hits of this screen. MK-5108, a highly selective inhibitor for AURKA (Aurora kinase A), induced YAP phosphorylation and cytoplasmic retention and significantly reduced profibrotic gene expression in human lung fibroblasts. The inhibitory effect on YAP nuclear translocation and profibrotic gene expression is specific to inhibition of AURKA, but not Aurora kinase B or C, and is independent of the Hippo pathway kinases LATS1 and LATS2 (Large Tumor Suppressor 1 and 2). Further characterization of the effects of MK-5108 demonstrate that it inhibits YAP nuclear localization indirectly via effects on actin polymerization and TGFβ (Transforming Growth Factor β) signaling. In addition, MK-5108 treatment reduced lung collagen deposition in the bleomycin mouse model of pulmonary fibrosis. Our results reveal a novel role for AURKA in YAP-mediated profibrotic activity in fibroblasts and highlight the potential of small-molecule screens for YAP inhibitors for identification of novel agents with antifibrotic activity.
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