Site-1 protease, a novel metabolic target for glioblastoma.

Sterol regulatory element binding proteins (SREBPs) are transcriptional regulators of lipids which promote glioblastoma growth. Here, we investigate the effect of inhibiting expression of SREBP target genes in human glioblastoma cells. This was achieved by using PF-429242 to inhibit site-1 protease (S1P), an enzyme required for SREBP activation. Treatment with PF-429242 decreased glioblastoma cell viability, induced apoptosis and downregulated steroid, isoprenoid and unsaturated fatty acid biosynthetic pathways. Several pro-inflammatory genes were upregulated. Collectively, these results demonstrate the potential of S1P as a target for glioblastoma therapy.