ArticleJCI insight2021
Direct conversion of osteosarcoma to adipocytes by targeting TNIK.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- The Impact of Targeting TRAF2 and NCK-Interacting Protein Kinase on Antitumor Effect and Tumor Immune Environment in c-MYC-High SCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- A system-wide investigation into the phosphoregulatory network of TNIK and its cellular implications.Frontiers in bioinformatics · 2026Article
- MAP4K signaling pathways in cancer: roles, mechanisms and therapeutic opportunities.Experimental & molecular medicine · 2025Review
- Identification of a TNIK-CDK9 Axis as a Targetable Strategy for Platinum-Resistant Ovarian Cancer.Molecular cancer therapeutics · 2025Article
- CLG promotes mTOR/ULK1 pathway-mediated autophagy to inhibit OS development by inhibiting TRAF6-mediated FLT3 ubiquitination.Cancer science · 2024Article
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Harnessing the potential of reverse-phase protein array technology: Advancing precision oncology strategies.Cancer science · 2024Review
- Expression analysis of TRAF2‑ and NCK‑interacting protein kinase (TNIK) and phosphorylated TNIK in papillary thyroid carcinoma.Oncology letters · 2023Article
- Identification of genes contributing to cisplatin resistance in osteosarcoma cells.FEBS open bio · 2023Article
- Chemoresistance-Related Stem Cell Signaling in Osteosarcoma and Its Plausible Contribution to Poor Therapeutic Response: A Discussion That Still Matters.International journal of molecular sciences · 2022Review
- Application of Multi-Omics Approach in Sarcomas: A Tool for Studying Mechanism, Biomarkers, and Therapeutic Targets.Frontiers in oncology · 2022Review
- Biological evidence of cancer stem-like cells and recurrent disease in osteosarcoma.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- BAIAP2L2 promotes the proliferation, migration and invasion of osteosarcoma associated with the Wnt/β-catenin pathway.Journal of bone oncology · 2021Article
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Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma (OS) is an aggressive mesenchymal tumor for which no molecularly targeted therapies are available. We have previously identified TRAF2- and NCK-interacting protein kinase (TNIK) as an essential factor for the transactivation of Wnt signal target genes and shown that its inhibition leads to eradication of colorectal cancer stem cells. The involvement of Wnt signaling in the pathogenesis of OS has been implicated. The aim of the present study was to examine the potential of TNIK as a therapeutic target in OS. RNA interference or pharmacological inhibition of TNIK suppressed the proliferation of OS cells. Transcriptome analysis suggested that a small-molecule inhibitor of TNIK upregulated the expression of genes involved in OS cell metabolism and downregulated transcription factors essential for maintaining the stem cell phenotype. Metabolome analysis revealed that this TNIK inhibitor redirected the metabolic network from carbon flux toward lipid accumulation in OS cells. Using in vitro and in vivo OS models, we confirmed that TNIK inhibition abrogated the OS stem cell phenotype, simultaneously driving conversion of OS cells to adipocyte-like cells through induction of PPARγ. In relation to potential therapeutic targeting in clinical practice, TNIK was confirmed to be in an active state in OS cell lines and clinical specimens. From these findings, we conclude that TNIK is applicable as a potential target for treatment of OS, affecting cell fate determination.
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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.