Targeting Wnt/β-catenin activation in combination with temozolomide leads to glioblastoma inhibition and long-term survival in mice.

ABSTRACT: Glioblastoma (GBM) is one of the most treatment-resistant brain malignancies. Dysregulation of Wnt/β-catenin signaling might be implicated in tumorigenesis of GBM. In this study, spatial transcriptomic analysis revealed elevated expression of Wnt target genes within tumor regions compared with peritumoral tissues. Overexpression of porcupine (PORCN), an O-acyltransferase for Wnt secretion, correlated with poor prognosis of GBM patients. Treatment with Wnt-C59, a PORCN inhibitor, inhibited Wnt signaling, hindered GBM cell proliferation and invasion, and inhibited GBM stem cells' self-renewal properties in a dose-dependent manner. Moreover, using β-catenin knockout and knockdown cells, FOXM1 was identified as a downstream transcription target of Wnt/β-catenin signaling. Wnt-C59 inhibited the

SUBMITTER: Zhang X 

PROVIDER: S-EPMC12552954 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature