ArticleThe Journal of clinical investigation2009
JNK1 determines the oncogenic or tumor-suppressive activity of the integrin-linked kinase in human rhabdomyosarcoma.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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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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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism.Nature · 2015Pooled it
- HDAC3 genetic and pharmacologic inhibition radiosensitizes fusion positive rhabdomyosarcoma by promoting DNA double-strand breaks.Cell death discovery · 2024Article
- JNK signaling as a target for anticancer therapy.Pharmacological reports : PR · 2021Review
- KDM3A/Ets1 epigenetic axis contributes to PAX3/FOXO1-driven and independent disease-promoting gene expression in fusion-positive Rhabdomyosarcoma.Molecular oncology · 2020Article
- Integrin-linked kinase controls retinal angiogenesis and is linked to Wnt signaling and exudative vitreoretinopathy.Nature communications · 2019Article
- Rsu1-dependent control of PTEN expression is regulated via ATF2 and cJun.Journal of cell communication and signaling · 2019Article
- EpCAM+ Liver Cancer Stem-Like Cells Exhibiting Autocrine Wnt Signaling Potentially Originate in Cirrhotic Patients.Stem cells translational medicine · 2017Article
- Integrin-linked kinase overexpression promotes epithelial-mesenchymal transition via nuclear factor-κB signaling in colorectal cancer cells.World journal of gastroenterology · 2016Article
- A signaling network stimulated by β2 integrin promotes the polarization of lytic granules in cytotoxic cells.Science signaling · 2014Article
- JNK signaling mediates EPHA2-dependent tumor cell proliferation, motility, and cancer stem cell-like properties in non-small cell lung cancer.Cancer research · 2014Article
- Review
- Dissecting integrin-dependent regulation of neural stem cell proliferation in the adult brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Stress-induced isoforms of MDM2 and MDM4 correlate with high-grade disease and an altered splicing network in pediatric rhabdomyosarcoma.Neoplasia (New York, N.Y.) · 2013Article
- Mutation in integrin-linked kinase (ILK(R211A)) and heat-shock protein 70 comprise a broadly cardioprotective complex.PloS one · 2013Article
- DYRK2 priming phosphorylation of c-Jun and c-Myc modulates cell cycle progression in human cancer cells.The Journal of clinical investigation · 2012Article
- JNK-induced apoptosis, compensatory growth, and cancer stem cells.Cancer research · 2012Review
- Advances in pediatric rhabdomyosarcoma characterization and disease model development.Histology and histopathology · 2012Review
- ILK induces cardiomyogenesis in the human heart.PloS one · 2012Article
- c-Jun N-terminal kinase is involved in the regulation of proliferation and apoptosis by integrin-linked kinase in human retinoblastoma cells.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2011Article
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Authors and funding
6 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although most reports describe the protein kinase integrin-linked kinase (ILK) as a proto-oncogene, occasional studies detail opposing functions in the regulation of normal and transformed cell proliferation, differentiation, and apoptosis. Here, we demonstrated that ILK functions as an oncogene in the highly aggressive pediatric sarcoma alveolar rhabdomyosarcoma (ARMS) and as a tumor suppressor in the related embryonal rhabdomyosarcoma (ERMS). These opposing functions hinge on signaling through a noncanonical ILK target, JNK1, to the proto-oncogene c-Jun. RNAi-mediated depletion of ILK induced activation of JNK and its target, c-Jun, resulting in growth of ERMS cells, whereas in ARMS cells, it led to loss of JNK/c-Jun signaling and suppression of growth both in vitro and in vivo. Ectopic expression of the fusion gene characteristic of ARMS (paired box 3-forkhead homolog in rhabdomyosarcoma [PAX3-FKHR]) in ERMS cells was sufficient to convert them to an ARMS signaling phenotype and render ILK activity oncogenic. Furthermore, restoration of JNK1 in ARMS reestablished a tumor-suppressive function for ILK. These findings indicate what we believe to be a novel effector pathway regulated by ILK, provide a mechanism for interconversion of oncogenic and tumor-suppressor functions of a single regulatory protein based on the genetic background of the tumor cells, and suggest a rationale for tailored therapy of rhabdomyosarcoma based on the different activities of ILK.
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