Contribution of the Wnt Pathway to Defining Biology of Glioblastoma

Glioblastoma (GBM), a highly lethal brain tumor, has been comprehensively characterized at the molecular level with the identification of several potential treatment targets. Data concerning the Wnt pathway are relatively sparse, but apparently very important in defining several aspects of tumor biology. The Wnt ligands are involved in numerous basic biological processes including regulation of embryogenic development, cell fate determination, and organogenesis, but growing amount of data also support the roles of Wnt pathways in the formation of many tumors, including gliomas. Two main Wnt pathways are distinguished: the canonical (-catenin) and non-canonical (planar cell polarity, Wnt/Ca2+) routes. Wnt signaling regulates glioma stem cells (GSCs), thereby defining invasive potential, recurrence, and treatment resistance of GBM. Some observations suggest that the Wnt pathways are differentially active in molecular subtypes of this tumor, thereby may also guide prognostication and novel therapeutic decisions. In this review, we highlight main elements and biological relevance of the Wnt pathways, primarily focusing on the pathogenesis and subtypes of GBM. Finally, we briefly summarize newer therapeutic strategies targeting networks of the Wnt signaling cascades and their molecular associates that appear to be marked contributors to GBM aggressiveness.