title: NF-κB-induced KIAA1199 promotes survival through EGFR signalling.
abstract: 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.
authors.affiliation: 1] Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [2] Laboratory of Medical Chemistry, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [3] GIGA-Signal Transduction, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium.
authors.forename: Kateryna
authors.initials: K
authors.lastname: Shostak
authors.affiliation: 1] Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [2] Laboratory of Medical Chemistry, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [3] GIGA-Signal Transduction, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 1] Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [2] Laboratory of Experimental Pathology, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [3] GIGA-Cancer, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium.
authors.forename: Pascale
authors.initials: P
authors.lastname: Hubert
authors.affiliation: 1] Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [2] Laboratory of Medical Chemistry, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [3] GIGA-Signal Transduction, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium.
authors.forename: Serkan Ismail
authors.initials: SI
authors.lastname: Göktuna
authors.affiliation: 1] Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [2] Laboratory of Medical Chemistry, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [3] GIGA-Signal Transduction, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium.
authors.forename: Zheshen
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: 1] Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [2] Laboratory of Medical Chemistry, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [3] GIGA-Signal Transduction, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium.
authors.forename: Iva
authors.initials: I
authors.lastname: Klevernic
authors.affiliation: 1] Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [2] Laboratory of Medical Chemistry, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [3] GIGA-Signal Transduction, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium.
authors.forename: Julien
authors.initials: J
authors.lastname: Hildebrand
authors.affiliation: 1] Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [2] Laboratory of Experimental Pathology, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [3] GIGA-Cancer, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Roncarati
authors.affiliation: 1] Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [2] GIGA Transcriptomics Facility, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: Hennuy
authors.affiliation: 1] Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [2] Laboratory of Medical Chemistry, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [3] GIGA-Signal Transduction, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Ladang
authors.affiliation: 1] Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [2] Laboratory of Experimental Pathology, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [3] GIGA-Cancer, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium.
authors.forename: Joan
authors.initials: J
authors.lastname: Somja
authors.affiliation: 1] Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [2] GIGA-Infection, Immunity and Inflammation, Department of Medicine/Hematology, University of Liege, CHU, Sart-Tilman, Liege 4000, Belgium.
authors.forename: André
authors.initials: A
authors.lastname: Gothot
authors.affiliation: 1] Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [2] Laboratory of Medical Chemistry, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [3] GIGA-Signal Transduction, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Close
authors.affiliation: 1] Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [2] Laboratory of Experimental Pathology, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [3] GIGA-Cancer, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Delvenne
authors.affiliation: 1] Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [2] Laboratory of Medical Chemistry, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [3] GIGA-Signal Transduction, University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium [4] Walloon Excellence in Life Sciences and Biotechnology (WELBIO) , University of Liege, 1, Avenue de l'ho^pital, CHU, Sart-Tilman, Liege 4000, Belgium.
authors.forename: Alain
authors.initials: A
authors.lastname: Chariot
mesh_terms: D000081242:B-Cell Lymphoma 3 Protein; D002470:Cell Survival; D004815:Epidermal Growth Factor / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D006821:Hyaluronoglucosaminidase; D015603:Keratinocytes / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D061986:MCF-7 Cells; D030361:Papillomavirus Infections / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D040121:Semaphorin-3A / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D002578:Uterine Cervical Dysplasia / Q000378:metabolism
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D011506:Proteins; D011518:Proto-Oncogene Proteins; C108639:SEMA3A protein, human; D040121:Semaphorin-3A; D051996:Transcription Factor RelA; D014157:Transcription Factors; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; C491433:CEMIP protein, human; D006821:Hyaluronoglucosaminidase