Disruption of β-catenin-mediated negative feedback reinforces cAMP-induced neuronal differentiation in glioma stem cells.

ABSTRACT: Accumulating evidence supports the existence of glioma stem cells (GSCs) and their critical role in the resistance to conventional treatments for glioblastoma multiforme (GBM). Differentiation therapy represents a promising alternative strategy against GBM by forcing GSCs to exit the cell cycle and reach terminal differentiation. In this study, we demonstrated that cAMP triggered neuronal differentiation and compromised the self-renewal capacity in GSCs. In addition, cAMP induced negative feedback to antagonize the differentiation process by activating β-catenin pathway. Suppression of β-catenin signaling synergized with cAMP activators to eliminate GSCs in vitro and extended the survival of animals in vivo. The cAMP/PKA pathway stabilized β-catenin through direct phosphorylation of the mo

SUBMITTER: Chen Z 

PROVIDER: S-EPMC9130142 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature