Deregulated expression of TANK in glioblastomas triggers pro-tumorigenic ERK1/2 and AKT signaling pathways
| Autor: | T Acker, Kateryna Shostak, S Ismail Göktuna, Julia Stellzig, Michael Schmitz, Florian Renner, Alain Chariot, Axel Pagenstecher |
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| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
TBK1 Kinase animal diseases glioblastoma technology industry and agriculture food and beverages Signal transducing adaptor protein TANK Cell cycle Biology NF-κB Cell biology ERK fluids and secretions Growth factor receptor TANK-binding kinase 1 inflammation Phosphorylation Original Article Signal transduction Molecular Biology Protein kinase B |
| Zdroj: | Oncogenesis |
| ISSN: | 2157-9024 |
| DOI: | 10.1038/oncsis.2013.42 |
| Popis: | Signal transmission by the noncanonical IkappaB kinases (IKKs), TANK-binding kinase 1 (TBK1) and IKKɛ, requires interaction with adapter proteins such as TRAF associated NF-κB activator (TANK). Although increased expression or dysregulation of both kinases has been described for a variety of human cancers, this study shows that deregulated expression of the TANK protein is frequently occurring in glioblastomas (GBMs). The functional relevance of TANK was analyzed in a panel of GBM-derived cell lines and revealed that knockdown of TANK arrests cells in the S-phase and prohibits tumor cell migration. Deregulated TANK expression affects several signaling pathways controlling cell proliferation and the inflammatory response. Interference with stoichiometrically assembled signaling complexes by overexpression or silencing of TANK prevented constitutive interferon-regulatory factor 3 (IRF3) phosphorylation. Knockdown of TANK frequently prevents constitutive activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). TANK-mediated ERK1/2 activation is independent from the canonical MAP kinase or ERK kinase (MEK) 1/2-mediated pathway and utilizes an alternative pathway that uses a TBK1/IKKɛ/Akt signaling axis, thus identifying a novel pathway suitable to block constitutive ERK1/2 activity. |
| Databáze: | OpenAIRE |
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