ArticleCancer medicine2019
TYK2 promotes malignant peripheral nerve sheath tumor progression through inhibition of cell death.
Article in Cancer medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- IFN signaling is associated with radiotherapy response in malignant peripheral nerve sheath tumors.The Journal of clinical investigation · 2026Article
- SS18-SSX drives TYK2 expression to activate STAT3/Bcl2 axis, facilitating apoptosis evasion and advancing synovial sarcoma progression.Cell biology and toxicology · 2024Article
- Malignant Peripheral Nerve Sheath Tumor, a Heterogeneous, Aggressive Cancer with Diverse Biomarkers and No Targeted Standard of Care: Review of the Literature and Ongoing Investigational Agents.Targeted oncology · 2024Review
- Functional interactions between neurofibromatosis tumor suppressors underlie Schwann cell tumor de-differentiation and treatment resistance.Nature communications · 2024Article
- Targeting TYK2 for Fighting Diseases: Recent Advance of TYK2 Inhibitors.Current medicinal chemistry · 2024Review
- MEK Inhibition Synergizes with TYK2 Inhibitors in NF1-Associated Malignant Peripheral Nerve Sheath Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- PRC2 loss drives MPNST metastasis and matrix remodeling.JCI insight · 2022Article
- Identification of Gene-Tyrosine Kinase 2 (TYK2) in Head and Neck Squamous Cell Carcinoma Patients-An Integrated Bioinformatics Approach.Disease markers · 2022Article
- Review
- Cirsiliol targets tyrosine kinase 2 to inhibit esophageal squamous cell carcinoma growth in vitro and in vivo.Journal of experimental & clinical cancer research : CR · 2021Article
- Diagnosis and management of malignant peripheral nerve sheath tumors: Current practice and future perspectives.Neuro-oncology advances · 2020Review
- Translating current basic research into future therapies for neurofibromatosis type 1.British journal of cancer · 2020Review
- From Genes to -Omics: The Evolving Molecular Landscape of Malignant Peripheral Nerve Sheath Tumor.Genes · 2020Review
- TYK2: An Upstream Kinase of STATs in Cancer.Cancers · 2019Review
- TYK2 promotes malignant peripheral nerve sheath tumor progression through inhibition of cell death.Cancer medicine · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundMalignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that arise most commonly in the setting of the Neurofibromatosis Type 1 (NF1) cancer predisposition syndrome. Despite aggressive multimodality therapy, outcomes are dismal and most patients die within 5 years of diagnosis. Prior genomic studies in our laboratory identified tyrosine kinase 2 (TYK2) as a frequently mutated gene in MPNST. Herein, we explored the function of TYK2 in MPNST pathogenesis.
methodsImmunohistochemistry was utilized to examine expression of TYK2 in MPNSTs and other sarcomas. To establish a role for TYK2 in MPNST pathogenesis, murine and human TYK2 knockdown and knockout cells were established using shRNA and CRISPR/Cas9 systems, respectively.
resultsWe have demonstrated that TYK2 was highly expressed in the majority of human MPNSTs examined. Additionally, we demonstrated that knockdown of Tyk2/TYK2 in murine and human MPNST cells significantly increased cell death in vitro. These effects were accompanied by a decrease in the levels of activated Stats and Bcl-2 as well as an increase in the levels of Cleaved Caspase-3. In addition, Tyk2-KD cells demonstrated impaired growth in subcutaneous and metastasis models in vivo.
conclusionTaken together, these data illustrate the importance of TYK2 in MPNST pathogenesis and suggest that the TYK2 pathway may be a potential therapeutic target for these deadly cancers.
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