KRAS Promotes GLI2-Dependent Transcription during Pancreatic Carcinogenesis.

ABSTRACT: Aberrant activation of GLI transcription factors has been implicated in the pathogenesis of different tumor types including pancreatic ductal adenocarcinoma. However, the mechanistic link with established drivers of this disease remains in part elusive. In this study, using a new genetically engineered mouse model overexpressing constitutively active mouse form of GLI2 and a combination of genome-wide assays, we provide evidence of a novel mechanism underlying the interplay between KRAS, a major driver of pancreatic ductal adenocarcinoma development, and GLI2 to control oncogenic gene expression. These mice, also expressing KrasG12D, show significantly reduced median survival rate and accelerated tumorigenesis compared with the KrasG12D only expressing mice. Analysis of the mechanism using

SUBMITTER: Sigafoos AN 

PROVIDER: S-EPMC11232480 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature