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<p>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).</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月15日

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  • Shaolin Liu,
  • Yizhen Chen,
  • Song Tan,
  • Yifan Chen,
  • Changshun Yang,
  • Yulong Mi,
  • Shengtao Lin,
  • Weihua Li

摘要

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).