Transgelin Promotes Glioblastoma Stem Cell Hypoxic Responses and Maintenance Through p53 Acetylation

Glioblastoma (GBM) is a lethal cancer characterized by hypervascularity and necrosis associated with hypoxia. Here, it is found that hypoxia preferentially induces the actin-binding protein, Transgelin (TAGLN), in GBM stem cells (GSCs). Mechanistically, TAGLN regulates HIF1 alpha transcription and stabilizes HDAC2 to deacetylate p53 and maintain GSC self-renewal. To translate these findings into preclinical therapeutic paradigm, it is found that sodium valproate (VPA) is a specific inhibitor of TAGLN/HDAC2 function, with augmented efficacy when combined with natural borneol (NB) in vivo. Thus, TAGLN promotes cancer stem cell survival in hypoxia and informs a novel therapeutic paradigm.

Automated summary

Hypoxia induces the expression of actin-binding protein Transgelin (TAGLN) in Glioblastoma stem cells (GSCs), promoting their survival and self-renewal through the regulation of HIF1α and stabilization of HDAC2. Sodium valproate (VPA), a specific inhibitor of TAGLN/HDAC2 function, shows enhanced efficacy when combined with natural borneol (NB) in vivo.