Media type: E-Article Title: IKKβ and NF-κB Transcription Govern Lymphoma Cell Survival through AKT-Induced Plasma Membrane Trafficking of GLUT1 Contributor: Sommermann, Thomas G.; O'Neill, Kathleen; Plas, David R.; Cahir-McFarland, Ellen Published: American Association for Cancer Research (AACR), 2011 Published in: Cancer Research, 71 (2011) 23, Seite 7291-7300 Language: English DOI: 10.1158/0008-5472.can-11-1715 ISSN: 0008-5472; 1538-7445 Origination: Footnote: Description: AbstractAll 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 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-κB inhibition repressed glucose uptake and induced caspase-independent cell death associated with autophagy. After NF-κB 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-κB signaling establishes a metabolic program supporting proliferation and apoptosis resistance by driving glucose import. Cancer Res; 71(23); 7291–300. ©2011 AACR. Access State: Open Access