Abstract 4756: N-cadherin signaling predicts prognosis in medulloblastoma subtypes

Identification of signaling pathways that drive the clinical behavior of tumors will guide specific molecular therapies. Medulloblastoma, the most common malignant pediatric solid tumor, shows considerable clinical and molecular diversity, providing impetus for specific targeted therapies of predicted molecular drivers. Here we show a gene signature derived from in vitro experimental inhibition of N-cadherin in medulloblastoma (MB) cells predicts survival in human MB in two large independent patient cohorts. Patients with high N-cadherin signature scores had earlier death and reduced overall survival. We found novel heterogeneity in proposed MB molecular subgroups, with significant differences in survival predicted by the N-cadherin signature in sonic hedgehog (SHH) and c2 tumors. In cultured MB cells, N-cadherin cell-cell interactions activated beta-catenin signaling and increased expression of the cancer stem cell regulator Sox2, known to be critical in the growth and relapse of SHH MB. Inhibition of N-cadherin reduced beta-catenin signaling and Sox2. Together, these findings indicate N-cadherin activity predicts the survival of patients with MB and suggest that differential activity of cellular pathways can identify novel disease subgroups and reveal molecular mechanisms with therapeutic significance. Citation Format: Maria Sverdlov, Michael P. Downing, Shuqi Kang, Anjen Chenn. N-cadherin signaling predicts prognosis in medulloblastoma subtypes. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4756.