ArticleProceedings of the National Academy of Sciences of the United States of America2003
Hyaluronidase 2 negatively regulates RON receptor tyrosine kinase and mediates transformation of epithelial cells by jaagsiekte sheep retrovirus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 93 citations in OpenAlex.
- Metabolic reprogramming, oxidative stress, and mitophagy in JSRV Env-transformed BEAS-2B cells: insights from integrated transcriptomics and metabolomics.BMC genomics · 2026Article
- Transcriptional Response of Ovine Lung to Infection with Jaagsiekte Sheep Retrovirus.Journal of virology · 2019Article
- Hypoxia-inducible factor 1α is Essential for Macrophage-mediated Erythroblast Proliferation in Acute Friend Retrovirus Infection.Scientific reports · 2017Article
- A human endogenous retrovirus-derived gene that can contribute to oncogenesis by activating the ERK pathway and inducing migration and invasion.PLoS pathogens · 2017Article
- Recent advances in the study of active endogenous retrovirus envelope glycoproteins in the mammalian placenta.Virologica Sinica · 2015Review
- Jaagsiekte sheep retrovirus detected in human lung cancer tissue arrays.BMC research notes · 2014Article
- Structural and functional comparisons of retroviral envelope protein C-terminal domains: still much to learn.Viruses · 2014Review
- Emerging roles for hyaluronidase in cancer metastasis and therapy.Advances in cancer research · 2014Review
- Hyaluronan, a crucial regulator of inflammation.Frontiers in immunology · 2014Review
- Pathogenesis of RON receptor tyrosine kinase in cancer cells: activation mechanism, functional crosstalk, and signaling addiction.Journal of biomedical research · 2013Review
- MSP-RON signalling in cancer: pathogenesis and therapeutic potential.Nature reviews. Cancer · 2013Review
- Analysis of jaagsiekte sheep retrovirus (JSRV) envelope protein domains in transformation.Virus genes · 2012Article
- Application of next generation sequencing in mammalian embryogenomics: lessons learned from endogenous betaretroviruses of sheep.Animal reproduction science · 2012Review
- Crystal structure of the Sema-PSI extracellular domain of human RON receptor tyrosine kinase.PloS one · 2012Article
- Article
- Enhanced proliferation of primary rat type II pneumocytes by Jaagsiekte sheep retrovirus envelope protein.Virology · 2011Article
- Jaagsiekte sheep retrovirus infects multiple cell types in the ovine lung.Journal of virology · 2011Article
- Jaagsiekte sheep retrovirus biology and oncogenesis.Viruses · 2010Article
- Endogenous retroviruses in trophoblast differentiation and placental development.American journal of reproductive immunology (New York, N.Y. : 1989) · 2010Review
- Friendly viruses: the special relationship between endogenous retroviruses and their host.Annals of the New York Academy of Sciences · 2009Article
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
The candidate tumor-suppressor gene hyaluronidase 2 (HYAL2) encodes a glycosylphosphatidylinositol-anchored cell-surface protein that serves as an entry receptor for jaagsiekte sheep retrovirus, a virus that causes contagious lung cancer in sheep that is morphologically similar to human bronchioloalveolar carcinoma. The viral envelope (Env) protein alone can transform cultured cells, and we hypothesized that Env could bind and sequester the HYAL2 receptor and thus liberate a potential oncogenic factor bound and negatively controlled by HYAL2. Here we show that the HYAL2 receptor protein is associated with the RON receptor tyrosine kinase (also called MST1R or Stk in the mouse), rendering it functionally silent. In human cells expressing a jaagsiekte sheep retrovirus Env transgene, the Env protein physically associates with HYAL2. RON liberated from the association with HYAL2 becomes functionally active and consequently activates the Akt and mitogen-activated protein kinase pathways leading to oncogenic transformation of immortalized human bronchial epithelial cells. We find activated RON in a subset of human bronchioloalveolar carcinoma tumors, suggesting RON involvement in this type of human lung cancer.
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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.