Smad4 and TGFβ1 dependent gene expression signatures in conditional intestinal adenoma, organoids and colorectal cancer.

ABSTRACT: TGF-β ligands suppress growth yet can paradoxically and potently promote cancer invasion and metastasis depending on downstream pathway mutational context, such as loss of Mothers against decapentaplegic homolog 4 (Smad4). Here, we characterised phenotypes and associated gene expression signatures in conditional murine intestinal adenoma with and without Smad4. Conditional Lgr5-CreER^T2 activation in Apc^fl/flSmad4^fl/fl mice resulted in homozygote floxed alleles (Apc^Δ/ΔSmad4^Δ/Δ) and adenoma formation. The adenoma phenotype was discordant, with reduced small intestinal adenoma burden yet development of large non-metastatic caecal adenoma with nuclear localisation of phospho-Smad2/3. Derived Apc^Δ/ΔSmad4^Δ/Δ adenoma org

SUBMITTER: Surakhy M 

PROVIDER: S-EPMC12065906 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature