ArticleMolecular cancer2022
Yap governs a lineage-specific neuregulin1 pathway-driven adaptive resistance to RAF kinase inhibitors.
Article in Molecular cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Nuclear PD-L1: an emerging oncogenic driver and promising therapeutic target in cancer.Journal of biomedical science · 2026Review
- Novel anti-HER2 nanobody-drug conjugates with enhanced penetration of solid tumor and BBB, reduced systemic exposure and superior antitumor efficacy.Acta pharmacologica Sinica · 2026Article
- Unravelling Resistance: Integrating Metabolism, Epigenetics, Immunology, and Proteostasis in Strategies against Kirsten Rat Sarcoma Viral Oncogene Homolog-mutant Colorectal Cancer.International journal of biological sciences · 2026Review
- Proteasome stress activates YAP/TAZ through the RAP2-MAP4Ks-LATS1/2 pathway and its therapeutic implications in solid tumors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- NOVEL INSIGHTS IN ADVANCED THYROID CARCINOMA: FROM MECHANISMS TO TREATMENTS: Molecular insights into the origin, biology, and treatment of anaplastic thyroid carcinoma.European thyroid journal · 2025Review
- The Revolution of Targeted Therapies in Thyroid Cancer Treatment: Present and Future Promising Anti-Cancer Drugs.International journal of molecular sciences · 2025Review
- Enhancing radioactive iodine (RAI) incorporation in RAI-refractory differentiated thyroid cancer: current insights.European thyroid journal · 2025Review
- BRAF-induced EHF Expression Affects TERT in Aggressive Papillary Thyroid Cancer.The Journal of clinical endocrinology and metabolism · 2025Article
- Development of animal models to study aggressive thyroid cancers.European thyroid journal · 2025Review
- Somatic copy number deletion of chromosome 22q in papillary thyroid carcinoma.European thyroid journal · 2025Article
- Expression and role of deubiquitinating enzymes in thyroid carcinoma.Briefings in functional genomics · 2025Review
- Positive feedback between arginine methylation of YAP and methionine transporter SLC43A2 drives anticancer drug resistance.Nature communications · 2025Article
- PDE4D drives rewiring of the MAPK pathway in BRAF-mutated melanoma resistant to MAPK inhibitors.Cell communication and signaling : CCS · 2024Article
- UBR1 promotes anaplastic thyroid carcinoma progression via stabilizing YAP through monoubiquitylation.Scientific reports · 2024Article
- Myeloid Cell-Derived IL-1 Signaling Damps Neuregulin-1 from Fibroblasts to Suppress Colitis-Induced Early Repair of the Intestinal Epithelium.International journal of molecular sciences · 2024Article
- BRAF - a tumour-agnostic drug target with lineage-specific dependencies.Nature reviews. Clinical oncology · 2024Review
- Genomic alterations in thyroid cancer: biological and clinical insights.Nature reviews. Endocrinology · 2024Review
- Extracellular cell matrix stiffness-driven drug resistance of breast cancer cells via EGFR activation.Mechanobiology in medicine · 2023Article
- New Insights into YAP/TAZ-TEAD-Mediated Gene Regulation and Biological Processes in Cancer.Cancers · 2023Review
- Progress in Thyroid Cancer Genomics: A 40-Year Journey.Thyroid : official journal of the American Thyroid Association · 2023Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundInactivation of the Hippo pathway promotes Yap nuclear translocation, enabling execution of a transcriptional program that induces tissue growth. Genetic lesions of Hippo intermediates only identify a minority of cancers with illegitimate YAP activation. Yap has been implicated in resistance to targeted therapies, but the mechanisms by which YAP may impact adaptive resistance to MAPK inhibitors are unknown.
methodsWe screened 52 thyroid cancer cell lines for illegitimate nuclear YAP localization by immunofluorescence and fractionation of cell lysates. We engineered a doxycycline (dox)-inducible thyroid-specific mouse model expressing constitutively nuclear YAP
resultsWe found that 27/52 thyroid cancer cell lines had constitutively aberrant YAP nuclear localization when cultured at high density (NU-YAP), which rendered them dependent on YAP for viability, invasiveness and sensitivity to the YAP-TEAD complex inhibitor verteporfin, whereas cells with confluency-driven nuclear exclusion of YAP (CYT-YAP) were not. Treatment of BRAF-mutant thyroid cancer cells with RAF kinase inhibitors resulted in YAP nuclear translocation and activation of its transcriptional output. Resistance to vemurafenib in BRAF-mutant thyroid cells was driven by YAP-dependent NRG1, HER2 and HER3 activation across all isogenic human and mouse thyroid cell lines tested, which was abrogated by silencing YAP and relieved by pan-HER kinase inhibitors. YAP activation induced analogous changes in BRAF melanoma, but not colorectal cells.
conclusionsYAP activation in thyroid cancer generates a dependency on this transcription factor. YAP governs adaptive resistance to RAF kinase inhibitors and induces a gene expression program in BRAF
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