Glioblastoma multiforme (GBM) is a highly aggressive brain cancer characterized by high rates of invasion and disease progression. While the importance of GBM cell-astrocyte gap junctions (GJ) in GBM invasion has been established, molecular mechanisms underlying GJ-mediated GBM invasion have yet to be determined. In their study on page 319, McCutcheon and Spray queried if Connexin 43 (Cx43), an astrocyte GJ protein expressed in nearly every GBM tumor, participates in GBM invasion. As pictured on the cover, the authors injected cytosolic mCherry-expressing GBM cells into ex vivo brain organotypic slice cultures and used immunofluorescence and confocal microscopy to assess GBM cell invasion. The cover depicts a GBM cell cluster with reduced invasion capacity in a brain slice in which astrocytes lack Cx43, where GBM cells are red, Cx43 is green, and cell nuclei are blue. Dichotomously, the authors found that Cx43 reduction in GBM cells increases GBM cell invasion. Altogether, the data elucidate novel molecular innerworkings of GBM cell invasion that could inform targeted GBM therapeutic strategies. This article is also Highlighted on page 181.