ArticleCancer research2023
WNT5a Signaling through ROR2 Activates the Hippo Pathway to Suppress YAP1 Activity and Tumor Growth.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Exploring STK3 in melanoma: a systematic review of signaling networks and therapeutic opportunities.Molecular biology reports · 2024Pooled it
- Review
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- MYOD1 mutation drives cancer stem cell pathways and therapy-resistance in spindle cell/sclerosing rhabdomyosarcoma.Nature communications · 2026Article
- NRG4 suppresses breast cancer metastasis via ERBB4-YAP1-mediated down-regulation of MMPs.Genes & diseases · 2026Article
- Wnt5a-Induced Exosomes From Bone Marrow Mesenchymal Stem Cells Promote Spinal Cord Injury Repair by Modulating Immune Cell Phenotypes and Alleviating Neuroinflammation via the NF-κB Pathway.CNS neuroscience & therapeutics · 2026Article
- Combined impact of ROR2 and its ligands on the pathogenesis and prognosis of idiopathic pulmonary fibrosis.Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG · 2026Article
- Mechanistic Insights and Therapeutic Potential of Wnt5a Signaling in Alveolar Epithelial Cell Development and Bronchopulmonary Dysplasia.Stem cell reviews and reports · 2025Review
- Ancestry-specific genetic effects on urinary 6-sulfatoxymelatonin: a multi-ancestry GWAS meta-analysis.Research square · 2025Article
- HOMER3 orchestrates SRC-YAP1 activity that promotes tumor cell growth and antagonizes anti-tumor immunotherapy in prostate cancer.Oncogene · 2025Article
- YAP as a therapeutic target to reverse trastuzumab resistance.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- Hypoxia-Driven Extracellular Vesicles Promote Pro-Metastatic Signalling in LNCaP Cells via Wnt and EMT Pathways.Biology · 2025Article
- Macrophage regulation of tumor cell dormancy and the dormant niche: an overview in solid tumors.Cancer metastasis reviews · 2025Review
- STK3 is a transcriptional target of YAP1 and a hub component in the crosstalk between Hippo and Wnt signaling pathways during gastric carcinogenesis.Molecular cancer · 2025Article
- LncRNA BDNF-AS binds to DNMT1 to suppress angiogenesis in glioma by promoting NEDD4L-mediated YAP1 ubiquitination.Molecular and cellular biochemistry · 2025Article
- Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications.Molecular cancer · 2025Review
- A-to-I-Edited miR-1304-3p Inhibits Glycolysis and Tumor Growth of Esophageal Squamous Cell Carcinoma by Inactivating Wnt5a/ROR2 Signaling.Molecular carcinogenesis · 2025Article
- HucMSCs-derived Exosomes Promote Lung Development in Premature Birth via Wnt5a/ROCK1 Axis.Stem cell reviews and reports · 2025Article
- Collective total synthesis of chartreusin derivatives and bioactivity investigations.Chemical science · 2025Article
- Construction and application of pancreatic exocrine organoid and spheroid for drug screening and precision medicine.Frontiers in cell and developmental biology · 2025Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Noncanonical Wnt signaling by WNT5a has oncogenic and tumor suppressive activities, but downstream pathways mediating these specific effects remain to be fully established. In a subset of prostate cancer organoid culture and xenograft models, inhibition of Wnt synthesis stimulated growth, whereas WNT5a or a WNT5a mimetic peptide (Foxy5) markedly suppressed tumor growth. WNT5a caused a ROR2-dependent decrease in YAP1 activity, which was associated with increased phosphorylation of MST1/2, LATS1, MOB1, and YAP1, indicating Hippo pathway activation. Deletion of MST1/2 abrogated the WNT5a response. WNT5a similarly activated Hippo in ROR2-expressing melanoma cells, whereas WNT5a in ROR2-negative cells suppressed Hippo. This suppression was associated with increased inhibitory phosphorylation of NF2/Merlin that was not observed in ROR2-expressing cells. WNT5a also increased mRNA encoding Hippo pathway components including MST1 and MST2 and was positively correlated with these components in prostate cancer clinical datasets. Conversely, ROR2 and WNT5a expression was stimulated by YAP1, and correlated with increased YAP1 activity in clinical datasets, revealing a WNT5a/ROR2 negative feedback loop to modulate YAP1 activity. Together these findings identify Hippo pathway activation as a mechanism that mediates the tumor suppressive effects of WNT5a and indicate that expression of ROR2 may be a predictive biomarker for responsiveness to WNT5a-mimetic drugs. SIGNIFICANCE: WNT5a signaling through ROR2 activates the Hippo pathway to downregulate YAP1/TAZ activity and suppress tumor growth, identifying ROR2 as a potential biomarker to identify patients that could benefit from WNT5a-related agents.
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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 OpenQuestion graph.