Glioblastoma is a highly aggressive brain tumor characterized by poor prognosis despite treatment with surgery, radiation, and chemotherapy. The tumor microenvironment (TME) of glioblastoma is complex, with modulatory interactions of glioblastoma cells with other TME cells ensuring dissemination and therapy resistance. Recent evidence suggests that glioblastoma cells lower their cAMP levels to enhance survival, and apoptotic death is induced by inhibiting phosphodiesterases (PDEs). Coronin 1 is an evolutionarily conserved protein that regulates cAMP/PKA signaling in neurons. Using immunohistochemistry and immunoblotting, we observed that coronin 1 is expressed in the neurons, glial cells, and the neuropil of the peri-tumoral normal brain regions. In the tumor region, coronin 1 is not expressed except for the resident and infiltrating immune cells and a subset of nestin-positive, CD133-positive, GFAP-positive, and SOX2-positive cells. To understand why coronin 1 is lost in glioblastoma tumor cells, coronin 1 was overexpressed in U87 and LN229 glioblastoma cells. Coronin 1-expressing glioblastoma cells showed reduced expression of Akt, calpain 2, PDE4, epithelial-to-mesenchymal transition (EMT)-like phenotype, invasion capacity, and extracellular matrix degradation. These results suggest that the loss of coronin 1 might play a pivotal role in modulating glioblastoma cell behavior by regulating invasion and EMT, potentially promoting a more aggressive phenotype. We hypothesize that coronin 1 downregulation contributes to the transition from undifferentiated to differentiated glioblastoma cells, supporting invasion and EMT-like phenotype. Further investigation of coronin 1's role in glioblastoma could offer novel therapeutic strategies for targeting tumor aggressiveness.
Keywords: EMT; GSCs; coronin 1; glioblastoma; invasion.
© 2025 International Society for Neurochemistry.