Pharmacological inhibition or small interfering NTSR1 treatment blocked glioblastoma cell cycle progression in the G1 phase with a concomitantly decreased expression of CDK6, CDK4, and c-Myc.
Thus, SUMO1-CDK6 conjugation constitutes a mechanism of cell cycle control and inhibition of this SUMOylation pathway may provide a strategy for treatment of glioblastoma.
Here, we combined functional genetic screens and comprehensive genomic analyses to identify CDK6 as a GBM oncogene that is required for proliferation and viability in a subset of GBM cell lines and tumors.
Other amplified regions containing well-known oncogenes in GBMs were also detected at 7p12 (EGFR), 7q21 (CDK6), 4q12 (PDGFRA), and 12q13-15 (MDM2 and CDK4).
No gene rearrangement or deletion was observed in the p19INK4d gene in these cell lines; however, expression of CDK4 and CDK6 was elevated relative to matched normal brain tissue in eight of 18 GBM tumours (44%).