Journal article

Publication year: 2013

Journal: Oncogenesis

Volume number: 2

ISSN: 2157-9024

Open access status: Gold

DOI Link: https://doi.org/10.1038/oncsis.2013.42

Publisher: Springer Nature [academic journals on nature.com]

Abstract: 
Signal transmission by the noncanonical IkappaB kinases (IKKs), TANK-binding kinase 1 (TBK1) and IKK kappa, requires interaction with adapter proteins such as TRAF associated NF-kappa B 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/IKK epsilon/Akt signaling axis, thus identifying a novel pathway suitable to block constitutive ERK1/2 activity.

Harvard Citation style: Stellzig, J., Chariot, A., Shostak, K., Goktuna, S., Renner, F., Acker, T., et al. (2013) Deregulated expression of TANK in glioblastomas triggers pro-tumorigenic ERK1/2 and AKT signaling pathways, Oncogenesis, 2, Article UNSP e79. https://doi.org/10.1038/oncsis.2013.42

APA Citation style: Stellzig, J., Chariot, A., Shostak, K., Goktuna, S., Renner, F., Acker, T., Pagenstecher, A., & Schmitz, M. (2013). Deregulated expression of TANK in glioblastomas triggers pro-tumorigenic ERK1/2 and AKT signaling pathways. Oncogenesis. 2, Article UNSP e79. https://doi.org/10.1038/oncsis.2013.42