Apc-deficient pituitary stem cells drive adamantinomatous craniopharyngioma through senescence-associated inflammation

ABSTRACT: Adamantinomatous craniopharyngiomas (aCPs) are intracranial neoplasms that arise in the sellar and suprasellar region, affecting the endocrine and nervous systems causing severe sequelae. Although most of aCPs are driven by somatic mutations in β-catenin (CTNNB1) some cases remain genetically unresolved. Here, we show that disruption of the Wnt-antagonist and tumour suppressor adenomatous polyposis coli (Apc) leads to pituitary tumours that present all classic molecular and histopathological hallmarks of aCPs. Mechanistically, we show that a hypomorphic allele of Apc leads to tumour development and that bi-allelic loss of Apc in the Sox2+ve pituitary stem cells can initiate aCP. Apc-driven tumour-initiating cells show a distinct transcriptional signature of p21-mediated senescence-associa

SUBMITTER: James Blackburn 

PROVIDER: S-SCDT-10_1038-S44321-026-00525-2 | biostudies-other |

REPOSITORIES: biostudies-other