Activation of survival signals in melanoma cells in response to glucose deprivation (766.9)

Abstract

Cancer’s use of alternate cellular pathways is necessary in order to proliferate and expand so aggressively but may make it possible to target using certain cancer therapies. We studied the effects that lowered glucose concentrations have on important cancer characteristics in WM266‐4 Melanoma cells. Changes to the cells included observable effects like morphology alteration and inhibition of growth as well as modification to internal signaling pathways. The cytoskeleton, being important for its interaction with insulin containing vesicles, altering of GLUT transporter translocation and glucose metabolism related enzymes, was disrupted after 48 hours which can be seen by the cells decreasing dendricity. Inhibition of growth was found to be correlated with decreasing glucose concentrations in medium, as was depletion of nutrients and changes in pH of the extracellular environment. Reduction in pH could be a mechanism of the cancer cells to proliferate and survive, the result of heavy production of lactic acid caused by increased rate of glycolysis, or both. Levels of p‐S6, p‐AMPK, p‐ERK and p‐MEK were shown to be increased by glucose deprivation at 6 hours showing that the cancer cells are fighting back in order to survive. S6 ribosomal protein as well p‐ACC decreased with glucose deprivation at 48 hours while p‐AMPK increased showing high levels of stress and eventually cellular shutdown. Finally, GLUT1 transporter expression as well as survivin, an anti‐apoptotic molecule, was shown to be increased at 24 hours under glucose deprivation. Collectively, our data suggest that the effects of glucose deprivation on melanoma are important in understanding the way these cells uptake their nutrients and may provide for therapeutic treatments in the future.Grant Funding Source: Supported by INBRE research grant