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RhoGTPases 和 Rho 效应物在肝细胞癌转移中的作用:ROCK N'Rho 推动其转移。

RhoGTPases and Rho-effectors in hepatocellular carcinoma metastasis: ROCK N'Rho move it.

机构信息

Liver Cancer and Hepatitis Research Laboratory, Department of Pathology, University of Hong Kong, Pokfulam, Hong Kong.

出版信息

Liver Int. 2010 May;30(5):642-56. doi: 10.1111/j.1478-3231.2010.02232.x.

Abstract

Hepatocellular carcinoma (HCC) is an intractable disease with an extremely high mortality rate. Metastasis is the major factor of liver failure, tumour recurrence and death in HCC patients. Unfortunately, no promising curative therapy for HCC metastasis is available as yet; therefore, treatment for advanced HCC still remains a formidable challenge. A large body of evidence has demonstrated that the RhoGTPases/Rho-effector pathway plays important roles in mediating HCC metastasis based on their foremost functions in orchestrating the cell cytoskeletal reorganization. This review will first discuss the general principles of cancer metastasis and cancer cell movement with a particular focus on HCC.We will then summarize the implications of various members in the RhoGTPases/Rho-effectors signalling cascade including the upstream RhoGTPase regulators RhoGTPases and Rho-effectors and their downstream targets in HCC metastasis. Finally, we will discuss the therapeutic insight of targeting the RhoGTPases/Rho-effector pathway in HCC. Taken together, the literature demonstrates the importance of the RhoGTPases/Rho-effector signalling pathway in HCC metastasis and marks the necessity to have a more thorough knowledge of this complicated signalling network in order to develop novel therapeutic strategies for HCC patients.

摘要

肝细胞癌(HCC)是一种死亡率极高的难治性疾病。转移是 HCC 患者肝衰竭、肿瘤复发和死亡的主要因素。不幸的是,目前尚无针对 HCC 转移的有前途的治愈疗法;因此,晚期 HCC 的治疗仍然是一个巨大的挑战。大量证据表明,RhoGTPases/Rho 效应子途径在介导 HCC 转移方面发挥着重要作用,这是基于它们在协调细胞细胞骨架重排方面的首要功能。本综述将首先讨论癌症转移和癌细胞运动的一般原则,特别关注 HCC。然后,我们将总结 RhoGTPases/Rho 效应子信号级联中的各种成员的意义,包括上游 RhoGTPase 调节剂 RhoGTPases 和 Rho 效应子及其在 HCC 转移中的下游靶点。最后,我们将讨论针对 RhoGTPases/Rho 效应子途径在 HCC 中的治疗意义。综上所述,文献证明了 RhoGTPases/Rho 效应子信号通路在 HCC 转移中的重要性,并标志着有必要更深入地了解这一复杂的信号网络,以便为 HCC 患者开发新的治疗策略。

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