NF-κB-induced KIAA1199 promotes survival through EGFR signalling
| العنوان: | NF-κB-induced KIAA1199 promotes survival through EGFR signalling |
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| المؤلفون: | Serkan Ismail Göktuna, Kateryna Shostak, Aurélie Ladang, Pierre Close, Patrick Roncarati, Joan Somja, Xin Zhang, Julien Hildebrand, Philippe Delvenne, Pascale Hubert, Iva Klevernic, Benoit Hennuy, Zheshen Jiang, Alain Chariot, André Gothot |
| المصدر: | Nature Communications |
| بيانات النشر: | Nature Pub. Group, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Keratinocytes, Epithelial-Mesenchymal Transition, Cell Survival, General Physics and Astronomy, Hyaluronoglucosaminidase, Biology, General Biochemistry, Genetics and Molecular Biology, Article, chemistry.chemical_compound, Semaphorin, Epidermal growth factor, B-Cell Lymphoma 3 Protein, Proto-Oncogene Proteins, Humans, Epithelial–mesenchymal transition, Transcription factor, Multidisciplinary, Epidermal Growth Factor, Kinase, Plexin, Papillomavirus Infections, Transcription Factor RelA, Proteins, NF-κB, Semaphorin-3A, General Chemistry, Uterine Cervical Dysplasia, ErbB Receptors, chemistry, Immunology, biology.protein, Cancer research, MCF-7 Cells, Lysosomes, Proto-oncogene tyrosine-protein kinase Src, HeLa Cells, Transcription Factors |
| الوصف: | Constitutive activation of EGFR- and NF-κB-dependent pathways is a hallmark of cancer, yet signalling proteins that connect both oncogenic cascades are poorly characterized. Here we define KIAA1199 as a BCL-3- and p65-dependent gene in transformed keratinocytes. KIAA1199 expression is enhanced on human papillomavirus (HPV) infection and is aberrantly expressed in clinical cases of cervical (pre)neoplastic lesions. Mechanistically, KIAA1199 binds Plexin A2 and protects from Semaphorin 3A-mediated cell death by promoting EGFR stability and signalling. Moreover, KIAA1199 is an EGFR-binding protein and KIAA1199 deficiency impairs EGF-dependent Src, MEK1 and ERK1/2 phosphorylations. Therefore, EGFR stability and signalling to downstream kinases requires KIAA1199. As such, KIAA1199 promotes EGF-mediated epithelial–mesenchymal transition (EMT). Taken together, our data define KIAA1199 as an oncogenic protein induced by HPV infection and constitutive NF-κB activity that transmits pro-survival and invasive signals through EGFR signalling. The cross-talk between constitutively active EGFR- and NF-κB-dependent pathways in cancer is poorly understood. Here, the authors identify KIAA1199 as a BCL3 and NF-κB-regulated protein that is expressed in cervical lesions and promotes tumorigenesis through Plexin A2 binding and regulation of EGFR stability. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c14e2715f119751ff7d625b5817be69eTest http://europepmc.org/articles/PMC4241993Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c14e2715f119751ff7d625b5817be69e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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