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Aerobic glycolysis is essential for supporting the fast growth of a variety of cancers. However, its role in the survival of cancer cells under stress conditions is unclear. We have previously reported an efficient model of gammaherpesvirus Kaposi’s sarcoma-associated herpesvirus (KSHV)-induced cellular transformation of rat primary mesenchymal stem cells. KSHV-transformed cells efficiently induce tumors in nude mice with pathological features reminiscent of Kaposi’s sarcoma tumors. Here, we report that KSHV promotes cell survival and cellular transformation by suppressing aerobic glycolysis and oxidative phosphorylation under nutrient stress. Specifically, KSHV microRNAs and vFLIP suppress glycolysis by activating the NF-κB pathway to downregulate glucose transporters GLUT1 and GLUT3. While overexpression of the transporters rescues the glycolytic activity, it induces apoptosis and reduces colony formation efficiency in softagar under glucose deprivation. Mechanistically, GLUT1 and GLUT3 inhibit constitutive activation of the AKT and NF-κB pro-survival pathways. Strikingly, GLUT1 and GLUT3 are significantly downregulated in KSHV-infected cells in human KS tumors. Furthermore, we have detected reduced levels of aerobic glycolysis in several KSHV-infected primary effusion lymphoma cell lines compared to a Burkitt’s lymphoma cell line BJAB, and KSHV infection of BJAB cells reduced aerobic glycolysis. These results reveal a novel mechanism by which an oncogenic virus regulates a key metabolic pathway to adapt to stress in tumor microenvironment, and illustrate the importance of fine-tuning the metabolic pathways for sustaining the proliferation and survival of cancer cells, particularly under stress conditions. [ABSTRACT FROM AUTHOR]

We synthetized a series of strontium-substituted submicron bioactive glasses spheres (Sr-SBG, SiO 2 -P 2 O 5 -CaO-SrO) in which strontium was substituted for calcium on a mole percentage basis, then investigated the effect of strontium-substituted amount on morphologies, physicochemical properties, apatite-forming bioactivity of SBG and evaluated the proliferation, differentiation and mineralization of Sr-SBG with different strontium substitution amounts by co-cultured with human dental pulp cells (HDPCs). Results showed that Sr-SBG with different strontium substitution amounts were successfully fabricated and substituting different strontium amounts did not affect the morphology and particle size of SBG. All the Sr-SBG possessed good apatite-forming ability, but substituting a certain amount of strontium for calcium would weaken the apatite-forming ability of SBG. Additionally, all the Sr-SBG extractions promoted proliferation, early odontogenic differentiation and mineralization of HDPCs, however, the cell proliferation, differentiation and mineralization abilities would be reduced when the substituted amount of strontium was excess (15 mol%). This study suggests that Sr-SBG with moderate strontium substitution amounts can be used as a more promising biomaterial for dental repair. [ABSTRACT FROM AUTHOR]