Figure 10

MYC confers metabolic flexibility in antiestrogen resistant cells. A, Rate of cell growth was significantly reduced in LCC9Gln cells compared with LCC9 control cells (p ≤ 0.001). Cell numbers at 72 h were compared using Student’s t test. B, MYC, MAX and GLUL protein levels were reduced, while GLS/GAC was increased, in LCC9Gln cells compared with control. C, Schematic diagram illustrating the role of MYC in regulating glutamine metabolism in complete (right; basal; with glucose and glutamine) and in glutamine-only conditions (left; glutamine but no glucose). MYC regulates glutamine, glutamate, and glucose uptake through transporters, ASCT2, EAAT2 and GLUT1, respectively, under normal conditions. In glucose-deprived conditions, glutamine metabolism triggers the UPR and induces cell death (inducing apoptosis and arresting autophagy) via a MYC-regulated IRE1α-JNK-CHOP in the short-term (72 h), and also promotes cell survival, through a IRE1α-XBP1(s); the surviving cells grow at a slower rate of cell proliferation (A), at >72 h. Dashed line denotes presence of intermediate metabolites/proteins that are not addressed in this study.