| First Author | Chiche J | Year | 2015 |
| Journal | Leukemia | Volume | 29 |
| Issue | 5 | Pages | 1163-76 |
| PubMed ID | 25394713 | Mgi Jnum | J:220619 |
| Mgi Id | MGI:5635743 | Doi | 10.1038/leu.2014.324 |
| Citation | Chiche J, et al. (2015) GAPDH enhances the aggressiveness and the vascularization of non-Hodgkin's B lymphomas via NF-kappaB-dependent induction of HIF-1alpha. Leukemia 29(5):1163-76 |
| abstractText | Deregulated expression of glycolytic enzymes contributes not only to the increased energy demands of transformed cells but also has non-glycolytic roles in tumors. However, the contribution of these non-glycolytic functions in tumor progression remains poorly defined. Here, we show that elevated expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), but not of other glycolytic enzymes tested, increased aggressiveness and vascularization of non-Hodgkin's lymphoma. Elevated GAPDH expression was found to promote nuclear factor-kappaB (NF-kappaB) activation via binding to tumor necrosis factor receptor-associated factor-2 (TRAF2), enhancing the transcription and the activity of hypoxia-inducing factor-1alpha (HIF-1alpha). Consistent with this, inactive mutants of GAPDH failed to bind TRAF2, enhance HIF-1 activity or promote lymphomagenesis. Furthermore, elevated expression of gapdh mRNA in biopsies from diffuse large B-cell non-Hodgkin's lymphoma patients correlated with high levels of hif-1alpha, vegf-a, nfkbia mRNA and CD31 staining. Collectively, these data indicate that deregulated GAPDH expression promotes NF-kappaB-dependent induction of HIF-1alpha and has a key role in lymphoma vascularization and aggressiveness. |
