Targeting the ARL4C/RAP1/PI3K-Akt-mTOR signaling loop promotes ARL4C ubiquitination and reverses oxaliplatin resistance in colorectal cancer.

ABSTRACT: Background: Oxaliplatin resistance poses a significant therapeutic challenge in colorectal cancer (CRC), contributing to disease progression and poor clinical outcomes. There is an urgent need to identify novel molecular targets to overcome chemoresistance and inhibit metastatic dissemination. Methods: We conducted integrative multi-omics analyses to identify genes associated with oxaliplatin resistance in CRC and detected ARL4C, a small GTPase, as a candidate driver. Functional experiments, including gene knockdown/overexpression, mutant construction, cell viability, apoptosis, migration, and invasion assays, as well as in vivo mouse models, were used to evaluate the role of ARL4C. Signaling pathways were examined using proteomics and molecular biology techniques. We

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12665106 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature