RhoA-ROCK2 signaling possesses complex pathophysiological functions in cancer progression and shows promising therapeutic potential.

IF 5.3 2区 医学 Q1 ONCOLOGY Cancer Cell International Pub Date : 2024-10-14 DOI:10.1186/s12935-024-03519-7
Yidi Ning, Minying Zheng, Yue Zhang, Yuqi Jiao, Jiangping Wang, Shiwu Zhang
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Abstract

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.

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RhoA-ROCK2 信号在癌症进展过程中具有复杂的病理生理功能,并显示出巨大的治疗潜力。
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、细胞分裂和特定基因的转录。RhoA和下游效应物ROCK2在癌症上皮-间充质转化、迁移、侵袭以及与干细胞相关的耐药性中的作用,凸显了靶向RhoA/ROCK2信号在治疗中的潜力。肿瘤复发可能是由于癌细胞对辅助化放疗、靶向治疗或免疫治疗没有完全反应。Rho 信号介导的有丝分裂缺陷和细胞分裂失败会导致细胞不对称分裂,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。在这篇综述中,我们阐明了 RhoA/ROCK2 在癌症进展机制中的重要作用,并总结了可改善治疗策略的抑制剂。
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来源期刊
CiteScore
10.90
自引率
1.70%
发文量
360
审稿时长
1 months
期刊介绍: Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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