biostudies-literatureLiu Sfinancial grants from the Natural Science Foundation of Fujian Province285https://www.ebi.ac.uk/biostudies/studies/S-EPMC12356972biostudies-literatureUnknown9(1)Rho GTPase-activating protein 4 (ARHGAP4) is implicated in poor prognosis across multiple malignancies. However, its role in driving stemness in colorectal cancer (CRC) remains unclear. In this study, we demonstrate that ARHGAP4 drives CRC stemness through a positive feedback loop involving MYH9/β-catenin/c-Jun, as validated by integrated bioinformatics analysis, in vitro and in vivo tumor stemness assays, co-immunoprecipitation, chromatin immunoprecipitation, and fluorescence recovery after photobleaching. These findings identify ARHGAP4 as a promising therapeutic target in CRC, particularly for addressing cancer stem cells (CSCs).NPJ precision oncologyARHGAP4/MYH9/β-catenin/c-Jun positive feedback loop promotes colorectal cancer stemness.PMC123569722022J011024Li WMi YLin STan SChen YLiu SYang CfalseARHGAP4/MYH9/β-catenin/c-Jun positive feedback loop promotes colorectal cancer stemness.Rho GTPase-activating protein 4 (ARHGAP4) is implicated in poor prognosis across multiple malignancies. However, its role in driving stemness in colorectal cancer (CRC) remains unclear. In this study, we demonstrate that ARHGAP4 drives CRC stemness through a positive feedback loop involving MYH9/β-catenin/c-Jun, as validated by integrated bioinformatics analysis, in vitro and in vivo tumor stemness assays, co-immunoprecipitation, chromatin immunoprecipitation, and fluorescence recovery after photobleaching. These findings identify ARHGAP4 as a promising therapeutic target in CRC, particularly for addressing cancer stem cells (CSCs).2025-01-01T00:00:00Z2025 Aug2026-07-01T03:12:14.841Z2026-07-01T03:07:13.453ZS-EPMC123569724081740410.1038/s41698-025-01022-4