KRAS silencing impacts chromatin organization and transcriptional activity in colorectal cancer cells.

ABSTRACT: Preclinical and clinical data have highlighted the challenges in targeting KRAS mutant tumors, revealing that cancer cells initially sensitive to treatment circumvent KRAS dependence and become tolerant. However, the exact mechanisms governing the transition from a drug-sensitive to a drug-tolerant state remain unclear. Herein, we used 3D culture models of mutant KRAS colorectal cancer cells with distinct KRAS dependencies to show that sensitive and resistant cells undergo distinct chromatin and transcriptional adaptations upon acute KRAS loss. KRAS-silenced sensitive cells presented G0/G1 cell cycle arrest and exhibited a transcriptional signature characteristic of quiescent cells. Moreover, proteomic profiling underscored common biological processes up-regulated in sensitive cells, inclu

SUBMITTER: Martins F 

PROVIDER: S-EPMC10896403 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature