e14045 Background: Glioblastoma multiforme (GBM) is the most commonly occurring and most lethal primary central nervous system tumor. Treatment for GBM involves an aggressive combination of surgical resection, radiotherapy, and temozolomide chemotherapy. While intensive therapy has shown marginal improvement in prognosis, the median survival for GBM patients remains between twelve to fourteen months. The aggressiveness of GBM is attributed to the cellular heterogeneity and the invasive nature of the tumor, as well as the presence of glioblastoma cancer stem cells (GSCs). GSCs are a subpopulation of slowly dividing cells within GBM tumors that can survive chemotherapy and irradiation treatments targeting proliferating cells. The remaining quiescent GSCs can then enter an active state of self-renewal and differentiation through asymmetric division that contributes to tumor recurrence by recapitulating the heterogeneous tumor in relatively short order. Previously, we have identified a non-junctional, tumorigenic function for the gap junction protein connexin43 (Cx43) through its interaction with microtubules in GSCs. However, when GSCs are differentiated, this interaction decreases while Cx43 expression increases, suggesting an alternate function for Cx43. Bone Morphogenic Proteins (BMPs) have been implicated in GSC differentiation and their role in human tumorigenesis has remained largely unknown in GSCs. In this study, we aim to determine the effect of BMP on Cx43 expression and localization in GSCs. Methods: In this study, we used GBM patient-derived GSCs isolated from two GBM tumors following resection at Carilion Clinic, and maintained in stem cell medium. The effect of BMP4 signaling on Cx43 expression and localization in GSCs was determined using RT-qPCR, immunofluorescence, western blot, and co-immunoprecipitation. Results: Preliminary data show that BMP4 treatment increases Cx43 expression at the protein and mRNA levels through nuclear translocation and transcriptional activity of β-catenin. In addition, BMP4 treatment increases the interaction between Cx43 and β-catenin at the plasma membrane. Further studies are underway to determine the implications of disrupting Cx43/β-catenin interaction in GSC differentiation. Conclusions: While additional experiments are needed, our findings may be adapted as a prognostic indicator to determine patients’ susceptibility to traditional GBM therapies, and aid in novel therapeutic development to eradicate GSCs in GBM and prevent tumor recurrence following treatment.