The repressor Capicua is a barrier to lung tumor development driven by Kras/Trp53 mutations

ABSTRACT: KRAS mutations are responsible for a quarter of all lung adenocarcinomas. However, the molecular mechanisms linking these mutations and their frequent secondary dosage amplification to tumor formation are still not fully understood. While ample evidence supports a crucial role for the MAPK pathway in tumor development, the primary effectors targeted by this pathway remain largely unexplored. Here we identify the transcriptional repressor Capicua (CIC) as a key target inactivated by KRAS/MAPK signaling in lung adenocarcinoma. We show that genetic loss of CIC recapitulates the phenotypic consequences of amplified KRAS signaling. Genetic disruption of CIC suppressed the requirement for Kras allelic imbalances and accelerated the transformation of bronchiolar Club cells. We also demonstrate th

SUBMITTER: Irene Ballesteros-González 

PROVIDER: S-SCDT-10_1038-S44321-025-00326-Z | biostudies-other |

REPOSITORIES: biostudies-other