Glucose starvation and hypoxia induce nuclear accumulation of proteasome in cancer cells.

ABSTRACT

Solid tumors commonly contain regions with glucose-starved and hypoxic conditions. Tumor cells under the adverse conditions can survive through the stress response, such as cell cycle arrest. In this study, we found that the stress conditions stimulated nuclear accumulation of proteasomes, large multicatalytic protease complexes, in human colon cancer HT-29 cells. The nuclear proteasome levels both in amount and in activity were increased approximately 4 and 2 times by glucose starvation and hypoxia, respectively. No changes were detected in the total expression levels of proteasome. The nuclear proteasome accumulation was also observed in ovarian cancer A2780 cells under glucose starvation, suggesting that this response was regardless of the origin of cancer cells. Our results indicate that the nuclear proteasome distribution is enhanced by glucose starvation and hypoxia, and suggest that the proteolysis by proteasome in the nucleus may play roles in the stress response of solid tumor cells.