Bcl9 and Pygo synergise downstream of Apc to effect intestinal neoplasia in FAP mouse models.

ABSTRACT: Bcl9 and Pygo are Wnt enhanceosome components that effect β-catenin-dependent transcription. Whether they mediate β-catenin-dependent neoplasia is unclear. Here we assess their roles in intestinal tumourigenesis initiated by Apc loss-of-function (Apc^Min), or by Apc^1322T encoding a partially-functional Apc truncation commonly found in colorectal carcinomas. Intestinal deletion of Bcl9 extends disease-free survival in both models, and essentially cures Apc^1322T mice of their neoplasia. Loss-of-Bcl9 synergises with loss-of-Pygo to shift gene expression within Apc-mutant adenomas from stem cell-like to differentiation along Notch-regulated secretory lineages. Bcl9 loss also promotes tumour retention in Apc^Min mice, apparently via relocating nuclear β

SUBMITTER: Mieszczanek J 

PROVIDER: S-EPMC6374407 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature