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IKK? and NF-?B transcription govern lymphoma cell survival through AKT-induced plasma membrane trafficking of GLUT1.


ABSTRACT: All cancer cells require increased nutrient uptake to support proliferation. In this study, we investigated the signals that govern glucose uptake in B-cell lymphomas and determined that the inhibitor of NF-?B-kinase ? (IKK?) induced glucose transporter-1 (GLUT1) membrane trafficking in both viral and spontaneous B-cell lymphomas. IKK? induced AKT activity, whereas IKK?-driven NF-?B transcription was required for GLUT1 surface localization downstream of AKT. Activated NF-?B promoted AKT-mediated phosphorylation of the GLUT1 regulator, AKT substrate of 160kD (AS160), but was not required for AKT phosphorylation of the mTOR regulator Tuberous Sclerosis 2 (TSC2). In Epstein-Barr virus-transformed B cells, NF-?B inhibition repressed glucose uptake and induced caspase-independent cell death associated with autophagy. After NF-?B inhibition, an alternate carbon source ameliorated both autophagy and cell death, whereas autophagy inhibitors specifically accelerated cell death. Taken together, the results indicate that NF-?B signaling establishes a metabolic program supporting proliferation and apoptosis resistance by driving glucose import.

SUBMITTER: Sommermann TG 

PROVIDER: S-EPMC3228879 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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IKKβ and NF-κB transcription govern lymphoma cell survival through AKT-induced plasma membrane trafficking of GLUT1.

Sommermann Thomas G TG   O'Neill Kathleen K   Plas David R DR   Cahir-McFarland Ellen E  

Cancer research 20111010 23


All cancer cells require increased nutrient uptake to support proliferation. In this study, we investigated the signals that govern glucose uptake in B-cell lymphomas and determined that the inhibitor of NF-κB-kinase β (IKKβ) induced glucose transporter-1 (GLUT1) membrane trafficking in both viral and spontaneous B-cell lymphomas. IKKβ induced AKT activity, whereas IKKβ-driven NF-κB transcription was required for GLUT1 surface localization downstream of AKT. Activated NF-κB promoted AKT-mediated  ...[more]

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