CSIG-11. ROLE OF OLIG2 PARTNER PROTEINS IN GLIOBLASTOMA

OLIG2 is a central nervous system specific transcription factor that is expressed in almost all diffuse gliomas. It is also one of the key core transcription factors that can reprogram differentiated glioma cells to highly tumorigenic glioma stem-like cells. We have previously shown that expression of OLIG2 is critical for glioma growth both in a genetically relevant mouse model as well as in patient-derived xenograft models. It is the phosphorylated form of OLIG2 (S10, S13 and S14) that is responsible for its pro-mitogenic functions. We have recently shown that OLIG2 interacts with distinct proteins based in its post-translational modifications. In an effort to identify direct interacting co-regulatory proteins of OLIG2 under oncogenic conditions we employed a novel proteomics screen, NAPPA (Nucleic Acid Programmable Protein Arrays). Using NAPPA analysis we have not only identified known interactors of OLIG2 (e.g., OLIG1, SALL2, p300 and HDAC1) but also novel interactors that have not been previously described. Here, we demonstrate how OLIG2 partners with distinct proteins to either promote proliferation or invasion in glioma stem-like cells based on its phosphorylation state. Furthermore, we provide evidence that targeting (genetic or pharmacological) of druggable OLIG2 partner proteins either alone or in combination with standard-of-care leads to significant decrease in growth of patient-derived xenograft models, both in vitro and in vivo.