Nuclear partitioning of Prohibitin 1 inhibits Wnt/β-catenin-dependent intestinal tumorigenesis.

ABSTRACT: The Wnt/β-catenin signaling pathway is aberrantly activated in the majority of colorectal cancer cases due to somatic mutations in the adenomatous polyposis coli (APC) gene. Prohibitin 1 (PHB1) serves pleiotropic cellular functions with dynamic subcellular trafficking, facilitating signaling crosstalk between organelles. Nuclear-localized PHB1 is an important regulator of gene transcription. Using mice with inducible intestinal epithelial cell (IEC)-specific deletion of Phb1 (Phb1^iΔIEC) and mice with IEC-specific overexpression of Phb1 (Phb1Tg), we demonstrate that IEC-specific PHB1 combats intestinal tumorigenesis in the Apc^Min/+ mouse model by inhibiting Wnt/β-catenin signaling. Forced nuclear accumulation of PHB1 in human RKO or SW48 CRC cell lines increased AXIN1

SUBMITTER: Alula KM 

PROVIDER: S-EPMC7856018 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature