Department of Urology, Shanghai East Hospital, Tongji University, Shanghai, 200120, China.
Department of Urology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, Shanghai, China.
Hum Cell. 2023 Mar;36(2):786-797. doi: 10.1007/s13577-023-00860-3. Epub 2023 Jan 30.
The Rho/ROCK pathway regulates diverse cellular processes and contributes to the development and advancement of several types of human cancers. This study investigated the role of specific Rho GTPase-activating proteins (RhoGAP), ARHGAP6, in bladder cancer (BC). In this study, ARHGAP6 expression in BC and its clinical significance were investigated. In vitro and in vivo assays were used to explore the tumor-related function and the underlying molecular mechanism ARHGAP6 of in BC. The mRNA and protein levels of ARHGAP6 significantly reduced in human BC tissues and cell lines compared with corresponding adjacent non-cancerous tissues and normal urothelial cells. In vitro, ARHGAP6 overexpression markedly decreased the viability, migration, and invasion of BC cells. Interestingly, low ARHGAP6 expression in BC strongly correlated with poor patient survival and was highly associated with metastasis and β-catenin signaling. Furthermore, ARHGAP6 expression strongly influenced the sensitivity of BC cells to mitomycin C treatment. Together, our results demonstrate that ARHGAP6 plays critical roles in regulating the proliferation, migration, invasion, and metastasis of BC cells possibly via the modulation of β-catenin and strongly influences the chemosensitivity of BC cells.
Rho/ROCK 通路调节多种细胞过程，并有助于几种类型的人类癌症的发展和进展。本研究探讨了特定 Rho GTPase 激活蛋白（RhoGAP），ARHGAP6，在膀胱癌（BC）中的作用。在这项研究中，研究了 ARHGAP6 在 BC 中的表达及其临床意义。使用体外和体内测定来探索 ARHGAP6 在 BC 中的肿瘤相关功能和潜在的分子机制。与相应的相邻非癌组织和正常尿路上皮细胞相比，ARHGAP6 的 mRNA 和蛋白水平在人 BC 组织和细胞系中明显降低。在体外，ARHGAP6 的过表达显着降低了 BC 细胞的活力，迁移和侵袭。有趣的是，BC 中低水平的 ARHGAP6 表达与患者预后不良强烈相关，并且与转移和β-连环蛋白信号密切相关。此外，ARHGAP6 的表达强烈影响 BC 细胞对丝裂霉素 C 治疗的敏感性。总之，我们的研究结果表明，ARHGAP6 通过调节β-连环蛋白在调节 BC 细胞的增殖，迁移，侵袭和转移中起关键作用，并强烈影响 BC 细胞的化疗敏感性。
