Differential unfolded protein response regulation in KRAS silencing sensitive and innately resistant colorectal cancer cells.

ABSTRACT: Despite the development of mutant-selective KRAS inhibitors, colorectal cancer (CRC) responses remain limited, with stable disease and rapid recurrence being common outcomes. The molecular mechanisms enabling CRC cells to tolerate KRAS inhibition and ultimately develop resistance remain poorly understood. Here, we investigated early transcriptional and proteomic responses to KRAS silencing in 3D CRC cell line spheroid models, aiming to identify pathways associated with sensitivity or resistance to KRAS blockade. Cell lines were stratified into KRAS silencing-sensitive (HCT116 and SW480) and -resistant (LS174T and SW837) groups based on spheroid growth, cell cycle progression, and apoptosis induction. Transcriptional profiling revealed the unfolded protein response (UPR) and WNT/β-catenin s

SUBMITTER: Martins F 

PROVIDER: S-EPMC12022182 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature