Ning Yidi, Zheng Minying, Zhang Yue, Jiao Yuqi, Wang Jiangping, Zhang Shiwu
Nankai University School of Medicine, Nankai University, Tianjin, 300071, P.R. China.
Department of Pathology, Tianjin Union Medical Center, Tianjin, 300121, P.R. China.
Cancer Cell Int. 2024 Oct 14;24(1):339. doi: 10.1186/s12935-024-03519-7.
The Rho GTPase signaling pathway is responsible for cell-specific processes, including actin cytoskeleton organization, cell motility, cell division, and the transcription of specific genes. The implications of RhoA and the downstream effector ROCK2 in cancer epithelial-mesenchymal transition, migration, invasion, and therapy resistance associated with stem cells highlight the potential of targeting RhoA/ROCK2 signaling in therapy. Tumor relapse can occur due to cancer cells that do not fully respond to adjuvant chemoradiotherapy, targeted therapy, or immunotherapy. Rho signaling-mediated mitotic defects and cytokinesis failure lead to asymmetric cell division, allowing cells to form polyploids to escape cytotoxicity and promote tumor recurrence and metastasis. In this review, we elucidate the significance of RhoA/ROCK2 in the mechanisms of cancer progression and summarize their inhibitors that may improve treatment strategies.
Rho GTPase信号通路负责细胞特异性过程，包括肌动蛋白细胞骨架组织、细胞运动、细胞分裂以及特定基因的转录。RhoA和下游效应分子ROCK2在癌症上皮-间质转化、迁移、侵袭以及与干细胞相关的治疗耐药性中的作用，凸显了在治疗中靶向RhoA/ROCK2信号通路的潜力。肿瘤复发可能是由于癌细胞对辅助放化疗、靶向治疗或免疫治疗没有完全反应所致。Rho信号介导的有丝分裂缺陷和胞质分裂失败会导致不对称细胞分裂，使细胞形成多倍体以逃避细胞毒性并促进肿瘤复发和转移。在本综述中，我们阐明了RhoA/ROCK2在癌症进展机制中的重要性，并总结了可能改善治疗策略的其抑制剂。
