Driver mutations of the adenoma-carcinoma sequence govern the intestinal epithelial global translational capacity.

ABSTRACT: Deregulated global mRNA translation is an emerging feature of cancer cells. Oncogenic transformation in colorectal cancer (CRC) is driven by mutations in APC, KRAS, SMAD4, and TP53, known as the adenoma-carcinoma sequence (ACS). Here we introduce each of these driver mutations into intestinal organoids to show that they are modulators of global translational capacity in intestinal epithelial cells. Increased global translation resulting from loss of Apc expression was potentiated by the presence of oncogenic Kras ^G12D Knockdown of Smad4 further enhanced global translation efficiency and was associated with a lower 4E-BP1-to-eIF4E ratio. Quadruple mutant cells with additional P53 loss displayed the highest global tran

SUBMITTER: Smit WL 

PROVIDER: S-EPMC7568276 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature