Di Jiehui, Zhao Zhongjun, Xia Mingyi, Gao Keyu, Chai Keli, Zhu Bao, Sun Wanping, Zhang Yanping, Zheng Junnian, Liu Yong
Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China.
Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou, Jiangsu, 221002, China.
Cell Death Dis. 2025 Apr 13;16(1):290. doi: 10.1038/s41419-025-07627-8.
Ras family protein plays a key role in transducing signals involved in cytoskeletal remodeling and cell adhesion, which are particularly important in the development of colorectal cancer (CRC). While Rap2B, a member of the Ras superfamily, has been linked to cancer malignancy in vitro, its exact role in tumorigenesis remains unclear. In this study, we demonstrated that intestine-specific knockout of Rap2B suppresses the initiation and progression of CRC. Mechanistically, Rap2B interacts with plectin and enhances its expression, which in turn inhibits plectin-mediated F-actin assembly. Deletion of Rap2B resulted in a remodeling of the intestinal cytoskeleton, leading to reduced tumorigenesis and diminished metastatic potential. Clinically, there is a positive correlation between the expression levels of Rap2B and plectin in human CRC tissues, and higher levels of Rap2B and plectin predicting poorer clinical outcome in CRC patients. These findings underscore a critical role of Rap2B in CRC progression and highlight its potential as a therapeutic target.
Ras家族蛋白在转导参与细胞骨架重塑和细胞黏附的信号中起关键作用，这在结直肠癌（CRC）的发展中尤为重要。虽然Ras超家族成员Rap2B在体外已被证明与癌症恶性程度有关，但其在肿瘤发生中的确切作用仍不清楚。在本研究中，我们证明肠道特异性敲除Rap2B可抑制CRC的起始和进展。机制上，Rap2B与网蛋白相互作用并增强其表达，进而抑制网蛋白介导的F-肌动蛋白组装。Rap2B的缺失导致肠道细胞骨架重塑，从而减少肿瘤发生并降低转移潜能。临床上，人类CRC组织中Rap2B和网蛋白的表达水平呈正相关，且Rap2B和网蛋白水平较高预示着CRC患者的临床预后较差。这些发现强调了Rap2B在CRC进展中的关键作用，并突出了其作为治疗靶点的潜力。
