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

ABSTRACT: EGF activates NF-?B, and constitutively activated NF-?B contributes to EGFR mutation-associated tumorigenesis, but it remains unclear precisely how EGFR signaling leads to NF-?B activation. Here we report that CARMA3, a caspase recruitment domain (CARD)-containing scaffold molecule, is required for EGF-induced NF-?B activation. CARMA3 deficiency impaired the activation of the IKK complex following EGF stimulation, resulting in a defect of EGF-induced I?B? phosphorylation and NF-?B 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.

SUBMITTER: Jiang T

PROVIDER: S-EPMC3059846 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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

Jiang Tang T Grabiner Brian B Zhu Yifan Y Jiang Changying C Li Hongxiu H You Yun Y Lang Jingyu J Hung Mien-Chie MC Lin Xin X

Cancer research 20110301 6

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 ...[more]

PMID: 21406399

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