The BAIAP2 Pathway Regulates Proliferation and Migration in Medulloblastoma.

Medulloblastoma (MB) is the most common malignant pediatric brain tumor, with high rates of recurrence and resistance to standard-of-care therapy. Therefore, novel drugs are needed that target different aspects of MB biology, including the proliferative and migratory properties of tumor cells. Using bioinformatic approaches, we demonstrate that the cytoskeletal scaffolding protein BAIAP2 is differentially expressed in MB compared to non-tumor brain cells, and that it is overexpressed in MB and metastatic MB tissue compared to normal cerebellum. BAIAP2 interacts with the Rho GTPases CDC42 and RAC1, which have known roles in migration and proliferation in multiple cell types. We demonstrate that BAIAP2 knockdown reduces migration and proliferation of MB cells. To characterize the BAIAP2 pathway further, we developed a small molecule screen using surface plasmon resonance (SPR) for compounds that bind BAIAP2. We discovered that the small molecule NSC678917 binds to BAIAP2 and inhibits MB cell proliferation and migration. Collectively, our studies suggest that the BAIAP2 pathway is a novel point of therapeutic intervention in MB.