Deregulated expression of TANK in glioblastomas triggers pro-tumorigenic ERK1/2 and AKT signaling pathways

[en] 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.

Research center :

Giga-Signal Transduction - ULiège

Disciplines :

Oncology

Author, co-author :

Stellzig, J

Chariot, Alain ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale

Shostak, Kateryna ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale

Göktuna, Serkan ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale

Renner, F

Acker, T

Pagenstecher, A

Schmitz, ML

Language :

English

Title :

Deregulated expression of TANK in glioblastomas triggers pro-tumorigenic ERK1/2 and AKT signaling pathways

Publication date :

11 November 2013

Journal title :

Observatoire (L')

ISSN :

0779-3677

Publisher :

Nature Publishing Group

Volume :

e79

Peer reviewed :

Peer reviewed

Funders :

WELBIO - Walloon Excellence in Life Sciences and Biotechnology [BE]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Télévie [BE]
Fondation contre le Cancer [BE]

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since 13 January 2014

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