TrkC binds to the type II TGF-β receptor to suppress TGF-β signaling
| العنوان: | TrkC binds to the type II TGF-β receptor to suppress TGF-β signaling |
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| المؤلفون: | Shin-Tae Kim, Chae-Ok Yun, Kwak Mk, Kim Ta, Jin W |
| المصدر: | Oncogene. 26:7684-7691 |
| بيانات النشر: | Springer Science and Business Media LLC, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Transcriptional Activation, Cancer Research, Small interfering RNA, animal structures, Receptor, Transforming Growth Factor-beta Type I, Smad2 Protein, Protein Serine-Threonine Kinases, Tropomyosin receptor kinase C, Mice, Transforming Growth Factor beta, Cell Line, Tumor, Genetics, Animals, Humans, Low-affinity nerve growth factor receptor, Gene silencing, Receptor, trkC, Smad3 Protein, RNA, Small Interfering, Molecular Biology, R-SMAD, biology, Tumor Suppressor Proteins, Receptor, Transforming Growth Factor-beta Type II, Molecular biology, Cell biology, nervous system, Trk receptor, NIH 3T3 Cells, biology.protein, Receptors, Transforming Growth Factor beta, Tyrosine kinase, Signal Transduction, Neurotrophin |
| الوصف: | Growing evidence suggests that overexpression of TrkC, a member of the Trk family of neurotrophin receptors, could drive tumorigenesis, invasion and metastatic capability in cancer cells. However, relatively little is known about the mechanism of TrkC-mediated oncogenesis. The TrkC gene is a partner of the Tel-TrkC (ETV6-NTRK3) chimeric tyrosine kinase, a potent oncoprotein expressed in tumors derived from multiple cell lineages. Recently, we have shown that ETV6-NTRK3 suppresses transforming growth factor-beta (TGF-beta) signaling by directly binding to the type II TGF-beta receptor (TbetaRII). Here, we report that expression of TrkC also suppresses TGF-beta-induced Smad2/3 phosphorylation and transcriptional activation. Silencing TrkC expression by small interfering RNA in the highly metastatic 4T1 mammary tumor cell line expressing endogenous TrkC significantly enhanced TGF-beta-induced Smad2/3 phosphorylation and restored TGF-beta growth inhibitory activity. In contrast, expression of TrkC in 67NR cells, in which TrkC is not expressed, suppressed TGF-beta transcriptional activation. Moreover, we show that TrkC directly binds to the TbetaRII, thereby preventing it from interacting with the type I TGF-beta receptor (TbetaRI). These results indicate that TrkC is an inhibitor of TGF-beta tumor suppressor activity. |
| تدمد: | 1476-5594 0950-9232 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c7bac327a6490f94383a947f88301869 https://doi.org/10.1038/sj.onc.1210571 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c7bac327a6490f94383a947f88301869 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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