Glioblastomas (GBMs) are invasive tumors with a poor prognosis; despite therapy with surgery, radiation, and chemotherapy, most patients die within 5 years. There is a need for therapies that address GBM’s resistance to treatment. Some of this resistance has been attributed to cancer stem cells (CSCs). CSCs are more invasive than non-CSCs and reside in niches that help maintain their stemness, and therefore maintain the tumor. Targeting the interaction between CSCs and their niche can provide a valuable novel therapy. Junctional adhesion molecule A (JAM-A), an adhesion molecule used by CSCs, was found to promote CSC maintenance, but its signaling pathways are not known. Studies investigating JAM-A binding partners identified SERPINB3, a protein associated with the transformation of normal epithelial cells to cancer cells. Given the oncogenic role of SERPINB3 and its binding with JAM-A, I hypothesized that SERPINB3 represents a key component of the signaling pathway in CSCs, driving GBM survival and growth. I confirmed that SERPINB3 is present in CSCs and coexpressed with JAM-A. I decreased SERPINB3 expression in CSCs and found that a stem cell marker, SOX2, also decreased. I increased SERPINB3 in CSCs and found that SOX2 transcript levels increased in response. Next I will test the effects of SERPINB3 levels on cell survival, growth, and self-renewal. This will help us gain a better understanding of how CSCs drive GBM survival and how to target them.