Divergent Roles of PI3K Isoforms in PTEN-Deficient Glioblastomas

• DOI: 10.1016/j.celrep.2020.108196
• Publication Date: 2020-09-29T14:36:33Z
• Authors: Shaozhen Xie; Jing Ni; J. Ricardo McFali...; Yanzhi Wang; Roderick T. Bronson; Keith L. Ligon; Patrick Y. Wen; Thomas M. Roberts; Jean J. Zhao
• Keywords: Male; 0301 basic medicine; Mice; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; PTEN Phosphohydrolase; Animals; Humans; Protein Isoforms; Glioblastoma; Article

Loss of PTEN, the negative regulator PI3K activity, is frequent in glioblastomas (GBMs). However, role two major isoforms, p110α and p110β, PTEN-deficient gliomagenesis remains unknown. We show that GBM largely depends on for proliferation p110β migration. Genetic ablation either isoform delays tumor progression mice, but only ablating both isoforms completely blocks driven by concurrent Pten p53. BKM120 (buparlisib) treatment modestly prolongs survival mice bearing intracranial Pten/p53 null tumors due to partial pathway inhibition. extends which not p110α, has been genetically ablated glioma, indicating fails inhibit effectively. Our study suggests failure inhibitors may be insufficient inhibition indicates a need develop brain-penetrant p110α/β inhibitors.