Rock2 promotes RCC proliferation by decreasing SCARA5 expression through β-catenin/TCF4 signaling

Rock2 promotes RCC proliferation by decreasing SCARA5 expression through β-catenin/TCF4 signaling
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Rock2 通过 β-catenin/TCF4 信号传导降低 SCARA5 表达,从而促进 RCC 增殖

DOI:
10.1016/j.bbrc.2016.10.097
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发表时间:
2016-11-25
影响因子:
3.1
通讯作者:
Shao, Jianghua
Shao, Jianghua
中科院分区:
生物学4区
文献类型:
--
作者:
Xu, Zheng;Hong, Zhengdong;Shao, Jianghua

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Rho 相关卷曲螺旋形成蛋白激酶 2 (Rock2) 作为小 GTP 酶 RhoA 的关键效应子,参与肿瘤的发展。 A 类清道夫受体成员 5 (SCARA5) 是癌细胞生物过程的重要调节因子。然而,Rock2 和 SCARA5 在肾细胞癌 (RCC) 中的作用和关系仍不清楚。在本研究中,我们发现与癌旁非癌组织相比,临床肾细胞癌组织中Rock2的表达显着升高。 Rock2的高表达与RCC患者的生存呈负相关,这表明Rock2可能是人类RCC的预后标志物。此外,Rock2 敲除增加了 SCARA5 表达,并在体外和体内抑制了 RCC 细胞增殖。此外,我们发现 β-catenin/TCF4 途径有助于 Rock2 对 SCARA5 介导的 RCC 增殖的影响。总而言之,这些结果表明,这个新发现的 Rock2-beta-catenin/TCF4-SCARA5 轴将为理解人类 RCC 增殖调节机制提供新的见解。 (C) 2016 Elsevier Inc. 保留所有权利。
Rho-associated coiled-coil forming protein kinase 2 (Rock2), as a key effector of the small GTPase RhoA, is involved in tumor development. Scavenger receptor class A member 5 (SCARA5) is an important regulator of biological processes in cancer cells. However, the roles and relationship of Rock2 and SCARA5 in renal cell carcinoma (RCC) remain unclear. In this study, we found that Rock2 expression was markedly increased in clinical RCC tissues compared with that in adjacent non-cancerous tissues. High expression of Rock2 was inversely correlated with patient survival in RCC, which indicated that Rock2 may be a prognostic marker in human RCC. In addition, Rock2 knockdown increased SCARA5 expression and suppressed RCC cell proliferation both in vitro and in vivo. Furthermore, we found that the beta-catenin/ TCF4 pathway contributed to the effect of Rock2 on SCARA5-mediated RCC proliferation. Taken together, these results suggest that this newly identified Rock2-beta-catenin/TCF4-SCARA5 axis will provide novel insight into the understanding of the regulatory mechanisms of proliferation in human RCC. (C) 2016 Elsevier Inc. All rights reserved.