ArticleNature communications2022
Hypoxia-activated neuropeptide Y/Y5 receptor/RhoA pathway triggers chromosomal instability and bone metastasis in Ewing sarcoma.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Neural-tumor interactions: bidirectional regulatory mechanisms and nervous system-targeted tumor therapeutic strategies.Biomarker research · 2026Review
- Chromosomal instability in cancer: sources, consequences and new therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Neuropeptide Y in cancer metastasis and chemoresistance.Neuropeptides · 2026Review
- Pro-neuropeptide Y as a circulating biomarker for poor prognosis in prostate cancer.Scientific reports · 2026Article
- Targeting Neuropeptide Y/DPP4 Signalling Suppresses Ewing Sarcoma Survival and Improves Monocyte Viability.International journal of molecular sciences · 2026Article
- From nerve to bone: a tale of autonomic nervous system, bone cells, and beyond.Military Medical Research · 2026Review
- The liver talks back: NPY orchestrates attraction of cancer cells and CHK2-dependent clonogenicity in the metastatic niche.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- GRPR-induced FAM135A expression promote perineural invasion in prostate cancer.Molecular cancer · 2025Article
- KC1036, a multi-kinase inhibitor with anti-angiogenic activity, can effectively suppress the tumor growth of Ewing sarcoma.Angiogenesis · 2025Article
- Targeted CRISPR approach reveals an essential role for neuropeptide Y receptor Y5 in Ewing sarcoma extrapulmonary metastasis.Oncogene · 2025Article
- TGFβ Inhibition during Radiotherapy Enhances Immune Cell Infiltration and Decreases Metastases in Ewing Sarcoma.Cancer research communications · 2025Article
- Ghrelin-induced neuronal NPY promotes brain metastasis in lung cancer patients with low BMI.Nature communications · 2025Article
- Targeting metastasis in paediatric bone sarcomas.Molecular cancer · 2025Review
- Single-Cell RNA Sequencing of Ewing Sarcoma Tumors Demonstrates Transcriptional Heterogeneity and Clonal Evolution.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- The neuroscience of cancer: Focus on neuropeptidergic systems.Acta pharmaceutica Sinica. B · 2025Review
- Targeting the NPY/NPY1R signaling axis in mutant p53-dependent pancreatic cancer impairs metastasis.Science advances · 2025Article
- Neuropeptide Y in cancer-biological functions and potential clinical implications.Cancer metastasis reviews · 2025Review
- Cilostazol-inhibited RhoA/NF-κB signaling mitigates hippocampal inflammation and post-stroke depression.Frontiers in pharmacology · 2025Article
- A novel histone acetylation-associated gene signature with prognostic value in Ewing sarcoma.Discover oncology · 2024Article
- RhoA-ROCK2 signaling possesses complex pathophysiological functions in cancer progression and shows promising therapeutic potential.Cancer cell international · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
25 authors.
Funding
Abstract
Adverse prognosis in Ewing sarcoma (ES) is associated with the presence of metastases, particularly in bone, tumor hypoxia and chromosomal instability (CIN). Yet, a mechanistic link between these factors remains unknown. We demonstrate that in ES, tumor hypoxia selectively exacerbates bone metastasis. This process is triggered by hypoxia-induced stimulation of the neuropeptide Y (NPY)/Y5 receptor (Y5R) pathway, which leads to RhoA over-activation and cytokinesis failure. These mitotic defects result in the formation of polyploid ES cells, the progeny of which exhibit high CIN, an ability to invade and colonize bone, and a resistance to chemotherapy. Blocking Y5R in hypoxic ES tumors prevents polyploidization and bone metastasis. Our findings provide evidence for the role of the hypoxia-inducible NPY/Y5R/RhoA axis in promoting genomic changes and subsequent osseous dissemination in ES, and suggest that targeting this pathway may prevent CIN and disease progression in ES and other cancers rich in NPY and Y5R.
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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.