Connexins: Bridging the gap between cancer cell communication in glioblastoma

Abstract

Despite concerted clinical and research efforts, glioblastoma (GBM), the most prevalent primary malignant brain tumor, remains uniformly lethal. Like other advanced cancers, GBM is characterized by extensive cellular heterogeneity and is organized in a hierarchy with self-renewing, therapeutically resistant cancer stem cells (CSCs) at the apex. While communication between GBM tumor cells and their surrounding stroma supports tumor survival and expansion, the mechanisms behind direct cell-cell communication and its contribution to tumor growth have yet to be fully elucidated. In particular, the biological importance of intercellular communication between GBM tumor cells, including CSCs and non-stem tumor cells (NSTCs) has yet to be determined. Gap junctions (GJs) are specialized structures, composed of connexin proteins, allowing for the diffusion of small molecules and ions directly between the cytoplasm of adjacent cells, enabling them to respond to each other and external stimuli rapidly and coordinately. Connexins have been found to help promote tumor cell growth, invasiveness, and tumorigenicity, making them attractive anti-tumor targets. However a complete understanding of the function of connexins and GJs in GBM remains an area of active investigation. Here we discuss recent advances in connexin function as they relate to our understanding of cellular communication and malignancy in GBM.