ARHGAP4/MYH9/β-连环蛋白/c-Jun正反馈回路促进结直肠癌干性。

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

作者信息

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

机构信息

Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.

Department of Gastrointestinal Surgery, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, China.

出版信息

NPJ Precis Oncol. 2025 Aug 15;9(1):285. doi: 10.1038/s41698-025-01022-4.

DOI:10.1038/s41698-025-01022-4

PMID:40817404

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).

摘要

Rho GTP酶激活蛋白4（ARHGAP4）与多种恶性肿瘤的不良预后有关。然而，其在驱动结直肠癌（CRC）干性方面的作用仍不清楚。在本研究中，我们通过综合生物信息学分析、体外和体内肿瘤干性测定、免疫共沉淀、染色质免疫沉淀以及光漂白后的荧光恢复验证，证明ARHGAP4通过涉及MYH9/β-连环蛋白/c-Jun的正反馈回路驱动CRC干性。这些发现确定ARHGAP4是CRC中一个有前景的治疗靶点，特别是用于解决癌症干细胞（CSCs）问题。