Figure 6. α₂M^*/CS-GRP78 signaling dictates aerobic glycolysis in an AKT dependent manner.

(A-B) Glucose consumption and lactate production were measured in indicated cancer cell lines stimulated either alone or in combination with α₂M^* (100 pM) for 30 min or acetate (5 mM) for 4 h in the absence and presence of ACLYi (100 μM) for 16 h, AKTi (GSK690693, 5 μM) for 16 h or C38 Mab (50 μg) for 6 h. mean ± SEM of triplicates. (C-D) Glucose consumption and lactate production were measured in the indicated cancer cell lines under normoxia or hypoxia were stimulated either alone or in combination with α₂M^* (100 pM) for 30 min or acetate (5 mM) for 4 h in the absence and presence of ACLYi (100 μM) for 16 h, AKTi (GSK690693, 5 μM/L) for 16 h or C38 Mab (50 μg) for 6 h. mean ± SEM of triplicates. (E) A model for α₂M^*/CS-GRP78 axis-dependent induction of histone acetylation. In addition to its ability to promote AKT pathway α₂M^*/CS-GRP78 axis also functions as a regulator of epigenetic metabolites to induce histone acetylation and tumor growth. Red arrow indicates that acetate regulates the AKT pathway through a feedback loop mechanism in a CS-GRP78 dependent manner. ^*, p values ≤ 0.05.