IKKβ and NF-κB Transcription Govern Lymphoma Cell Survival through AKT-Induced Plasma Membrane Trafficking of GLUT1
- 29 November 2011
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 71 (23), 7291-7300
- https://doi.org/10.1158/0008-5472.can-11-1715
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-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.Keywords
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