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ARHGAP4/MYH9/β-catenin/c-Jun positive feedback loop promotes colorectal cancer stemness.

ABSTRACT: 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).

SUBMITTER: Liu S 

PROVIDER: S-EPMC12356972 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature

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ARHGAP4/MYH9/β-catenin/c-Jun positive feedback loop promotes colorectal cancer stemness.

Liu Shaolin S   Chen Yizhen Y   Tan Song S   Chen Yifan Y   Yang Changshun C   Mi Yulong Y   Lin Shengtao S   Li Weihua W  

NPJ precision oncology 20250815 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 pho  ...[more]