Fu Junjie, Liu Bo, Zhang Hao, Fu Fangmei, Yang Xiaohui, Fan Linlin, Zheng Minying, Zhang Shiwu
Graduate School, Tianjin Medical University, Tianjin, 300070, P.R. China.
Department of Pathology, Tianjin Union Medical Center, Tianjin, P.R. China.
J Cancer. 2022 Jan 1;13(3):800-814. doi: 10.7150/jca.65415. eCollection 2022.
Rho-GTPases control a variety of cellular functions mainly by regulating microtubule and actin dynamics, affecting the cytoskeleton, and are important regulators of the structural plasticity of dendrites and spines. Members of the Rho-GTPase family include Ras-related C3 botulinum toxin substrate 1 (Rac1), RhoA (Ras homologous), and cell division control protein 42 (Cdc42). Cdc42 is involved in the regulation of a variety of tumor and non-tumor diseases through a cascade of multiple signaling pathways. Active Cdc42 can regulate intercellular adhesion, cytoskeleton formation, and cell cycle, thus affecting cell proliferation, transformation, and dynamic balance as well as migration and invasion of tumor cells by regulating the expression of effector proteins. Here we discuss the role of Cdc42 in promoting metastasis, invasion, epithelial-mesenchymal transformation and angiogenesis in malignant tumors. The significant role of Cdc42 in non-tumor diseases is also discussed. Since Cdc42 plays a central role in the development of various diseases, small molecule inhibitors targeting Cdc42 have important clinical significance in the prevention and treatment of these diseases.
Rho-GTP酶主要通过调节微管和肌动蛋白动力学、影响细胞骨架来控制多种细胞功能，并且是树突和棘突结构可塑性的重要调节因子。Rho-GTP酶家族成员包括Ras相关的C3肉毒杆菌毒素底物1（Rac1）、RhoA（Ras同源物）和细胞分裂控制蛋白42（Cdc42）。Cdc42通过一系列多重信号通路参与多种肿瘤和非肿瘤疾病的调控。活性Cdc42可调节细胞间黏附、细胞骨架形成和细胞周期，从而通过调节效应蛋白的表达影响细胞增殖、转化和动态平衡以及肿瘤细胞的迁移和侵袭。在此，我们讨论Cdc42在促进恶性肿瘤转移、侵袭、上皮-间质转化和血管生成中的作用。还讨论了Cdc42在非肿瘤疾病中的重要作用。由于Cdc42在各种疾病的发展中起核心作用，靶向Cdc42的小分子抑制剂在这些疾病的预防和治疗中具有重要的临床意义。
