ArticleThe Journal of biological chemistry2016
Tankyrase Inhibitor Sensitizes Lung Cancer Cells to Endothelial Growth Factor Receptor (EGFR) Inhibition via Stabilizing Angiomotins and Inhibiting YAP Signaling.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 78 citations in OpenAlex.
- Patient-derived AMOTL1 mutations lead to defective cell migration and tissue development.Bioscience reports · 2026Article
- Tankyrases and Their Binding Proteins: Origins of Their Roles in Diverse Cellular Pathways.Cells · 2026Review
- It's all downstream from here: RTK/Raf/MEK/ERK pathway resistance mechanisms in glioblastoma.Journal of neuro-oncology · 2025Review
- PARylation-mediated post-transcriptional modifications in cancer immunity and immunotherapy.Frontiers in immunology · 2025Review
- Tankyrase 2 promotes lung cancer cell malignancy.World journal of clinical oncology · 2024Article
- YAP, TAZ, and Hippo-Dysregulating Fusion Proteins in Cancer.Annual review of cancer biology · 2024Article
- Tankyrase inhibition interferes with junction remodeling, induces leakiness, and disturbs YAP1/TAZ signaling in the endothelium.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Role of YAP Signaling in Regulation of Programmed Cell Death and Drug Resistance in Cancer.International journal of biological sciences · 2024Review
- Modern therapies of nonsmall cell lung cancer.Journal of applied genetics · 2023Review
- Complex roles of Hippo-YAP/TAZ signaling in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2023Review
- Proteolytic activation of angiomotin by DDI2 promotes angiogenesis.The EMBO journal · 2023Article
- Wnt signaling preserves progenitor cell multipotency during adipose tissue development.Nature metabolism · 2023Article
- Article
- Review
- Blocking PI3K p110β Attenuates Development of PTEN-Deficient Castration-Resistant Prostate Cancer.Molecular cancer research : MCR · 2022Article
- Overexpression of miR-375 and L-type Amino Acid Transporter 1 in Pheochromocytoma and Their Molecular and Functional Implications.International journal of molecular sciences · 2022Article
- Cell adhesion molecule KIRREL1 is a feedback regulator of Hippo signaling recruiting SAV1 to cell-cell contact sites.Nature communications · 2022Article
- Evolution of Molecular Targeted Cancer Therapy: Mechanisms of Drug Resistance and Novel Opportunities Identified by CRISPR-Cas9 Screening.Frontiers in oncology · 2022Review
- Deubiquitination of TNKS1 Regulates Wnt/Disease markers · 2022Article
- Identification of response signatures for tankyrase inhibitor treatment in tumor cell lines.iScience · 2021Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
YAP signaling pathway plays critical roles in tissue homeostasis, and aberrant activation of YAP signaling has been implicated in cancers. To identify tractable targets of YAP pathway, we have performed a pathway-based pooled CRISPR screen and identified tankyrase and its associated E3 ligase RNF146 as positive regulators of YAP signaling. Genetic ablation or pharmacological inhibition of tankyrase prominently suppresses YAP activity and YAP target gene expression. Using a proteomic approach, we have identified angiomotin family proteins, which are known negative regulators of YAP signaling, as novel tankyrase substrates. Inhibition of tankyrase or depletion of RNF146 stabilizes angiomotins. Angiomotins physically interact with tankyrase through a highly conserved motif at their N terminus, and mutation of this motif leads to their stabilization. Tankyrase inhibitor-induced stabilization of angiomotins reduces YAP nuclear translocation and decreases downstream YAP signaling. We have further shown that knock-out of YAP sensitizes non-small cell lung cancer to EGFR inhibitor Erlotinib. Tankyrase inhibitor, but not porcupine inhibitor, which blocks Wnt secretion, enhances growth inhibitory activity of Erlotinib. This activity is mediated by YAP inhibition and not Wnt/β-catenin inhibition. Our data suggest that tankyrase inhibition could serve as a novel strategy to suppress YAP signaling for combinatorial targeted therapy.
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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.