Background
PPP2R2C encodes a gamma isoform of the regulatory subunit B55 subfamily consisting PP2A heterotrimeric with A and C subunits. Currently, the precise functions of B55gamma in cancer are still under investigating. In this project, we reported a novel function of B55gamma in the regulation of glucose metabolism in Glioma cells.
Conclusion
In summary, our project will provide novel insight into the design and development of therapeutic strategies to target the B55gamma-mediated glucose metabolism for the treatment of human brain tumor patients.
Methods
Western blot and immunoprecipitation were performed to determine protein expression and interaction. Cell viability was measured by Typan Blue staining and direct cell counting using hematocytometer. siRNA technology was used to down regulate protein expression.
Results
Glucose uptake and lactate product were suppressed by overexpression of B55gamma in Glioma cells. In addition, cancer cells with larger amount of B55gamma showed higher survival advantages in response to glucose starvation through the dephosphorylation of S6K. From proteomic analysis, we found B55gamma binds with and up regulates SIK2 through the stabilization of SIK2 protein which is required for the B55gamma-mediated suppression of S6K pathway. Knocking down of SIK2 in B55gamma over expressing cells recovered the phosphorylation of S6K.