Sequential Accumulation of 'Driver' Pathway Mutations Induces the Upregulation of Hydrogen-Sulfide-Producing Enzymes in Human Colonic Epithelial Cell Organoids.

ABSTRACT: Recently, a CRISPR-Cas9 genome-editing system was developed with introduced sequential 'driver' mutations in the WNT, MAPK, TGF-β, TP53 and PI3K pathways into organoids derived from normal human intestinal epithelial cells. Prior studies have demonstrated that isogenic organoids harboring mutations in the tumor suppressor genes APC, SMAD4 and TP53, as well as the oncogene KRAS, assumed more proliferative and invasive properties in vitro and in vivo. A separate body of studies implicates the role of various hydrogen sulfide (H₂S)-producing enzymes in the pathogenesis of colon cancer. The current study was designed to determine if the sequential mutations in the above pathway affect the expression of various H₂S producing enzymes. Western blotting was used to detect the

SUBMITTER: Ascencao K 

PROVIDER: S-EPMC9495861 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature