Msi1 integrates APC loss and mTORC1 activation to promote intestinal stem cell transformation

ABSTRACT: Loss of the APC tumor suppressor in the intestinal epithelium initiates the majority of human colorectal adenocarcinomas. Constitutive β-catenin activation is thought to underlie tumorigenesis induced by loss of APC, however β-catenin activation alone does not recapitulate all APC-loss phenotypes, suggesting that additional pathways are required. We demonstrate that aberrant activation of the Msi1 RNA binding protein occurs upon APC loss and that constitutive Msi1 activation alone is sufficient to phenocopy APC loss in the intestinal epithelium. Msi1 elicits these effects through binding of mRNAs encoding pleiotropic tumor suppressors resulting in promiscuous activation of quiescent intestinal stem cells, proliferative expansion of the stem cell compartment, crypt fission, and blocked di

ORGANISM(S): Mus musculus

SUBMITTER: Christopher Lengner 

PROVIDER: E-GEOD-54598 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress