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Cancer Res. 2011 Mar 15;71(6):2183-92. doi: 10.1158/0008-5472.CAN-10-3626.

CARMA3 is crucial for EGFR-Induced activation of NF-κB and tumor progression.

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  • 1Department of Molecular and Cellular Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas 77030, USA.

Abstract

EGF activates NF-κB, and constitutively activated NF-κB contributes to EGFR mutation-associated tumorigenesis, but it remains unclear precisely how EGFR signaling leads to NF-κB activation. Here we report that CARMA3, a caspase recruitment domain (CARD)-containing scaffold molecule, is required for EGF-induced NF-κB activation. CARMA3 deficiency impaired the activation of the IKK complex following EGF stimulation, resulting in a defect of EGF-induced IκBα phosphorylation and NF-κB activation. We found that CARMA3 and Bcl10 contributed to several characteristics of EGFR-associated malignancy, including proliferation, survival, migration, and invasion. Most importantly, CARMA3 contributed to tumor growth in vivo. Our findings elucidate a crucial link between EGFR-proximal signaling components and the downstream IKK complex, and they suggest a new therapeutic target for treatment of EGFR-driven cancers.

©2011 AACR.

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