Cancer Research Center of Toulouse, INSERM UMR1037, 31037 Toulouse, France.
Faculty of Pharmacy and Medecine, Université Toulouse III, 31062 Toulouse, France.
Int J Mol Sci. 2019 Jul 24;20(15):3612. doi: 10.3390/ijms20153612.
The Rho GTPase family can be classified into classic and atypical members. Classic members cycle between an inactive Guanosine DiPhosphate -bound state and an active Guanosine TriPhosphate-bound state. Atypical Rho GTPases, such as RND1, are predominantly in an active GTP-bound conformation. The role of classic members in oncogenesis has been the subject of numerous studies, while that of atypical members has been less explored. Besides the roles of RND1 in healthy tissues, recent data suggest that RND1 is involved in oncogenesis and response to cancer therapeutics. Here, we present the current knowledge on RND1 expression, subcellular localization, and functions in healthy tissues. Then, we review data showing that RND1 expression is dysregulated in tumors, the molecular mechanisms involved in this deregulation, and the role of RND1 in oncogenesis. For several aggressive tumors, RND1 presents the features of a tumor suppressor gene. In these tumors, low expression of is associated with a bad prognosis for the patients. Finally, we highlight that expression is induced by anticancer agents and modulates their response. Of note, mRNA levels in tumors could be used as a predictive marker of both patient prognosis and response to anticancer agents.
Rho GTPase 家族可分为经典和非典型成员。经典成员在非活性鸟苷二磷酸（GDP）结合态和活性鸟苷三磷酸（GTP）结合态之间循环。非典型 Rho GTPases，如 RND1，主要处于活性 GTP 结合构象。经典成员在肿瘤发生中的作用已成为众多研究的主题，而非典型成员的作用则较少被探索。除了 RND1 在健康组织中的作用外，最近的数据表明 RND1 参与了肿瘤发生和对癌症治疗的反应。在这里，我们介绍了目前关于 RND1 在健康组织中的表达、亚细胞定位和功能的知识。然后，我们回顾了表明 RND1 在肿瘤中表达失调的数据，涉及这种失调的分子机制，以及 RND1 在肿瘤发生中的作用。对于一些侵袭性肿瘤，RND1 表现出肿瘤抑制基因的特征。在这些肿瘤中， 的低表达与患者预后不良相关。最后，我们强调指出， 表达受抗癌药物诱导，并调节其反应。值得注意的是，肿瘤中的 mRNA 水平可作为患者预后和对抗癌药物反应的预测标志物。
