Tokunaga Eriko, Oki Eiji, Egashira Akinori, Sadanaga Noriaki, Morita Masaru, Kakeji Yoshihiro, Maehara Yoshihiko
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Curr Cancer Drug Targets. 2008 Feb;8(1):27-36. doi: 10.2174/156800908783497140.
Akt (protein kinase B) is a serine/threonine kinase which is a central regulator of widely divergent cellular processes including proliferation, differentiation, migration, survival and metabolism. Akt is activated by a variety of stimuli, through growth factor receptors, in phosphatidylinositol 3-kinase (PI3K)-dependent manner. Akt is also negatively regulated by the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN). A disruption of normal Akt/PKB/PTEN signaling frequently occurs in many human cancers, which plays an important role in cancer development, progression and therapeutic resistance. Numerous studies have revealed the blockage of Akt signaling to result in apoptosis and growth inhibition of tumor cells. Therefore, this signaling pathway, including both upstream and downstream of Akt, has recently attracted considerable attention as a new target for effective cancer therapeutic strategies. In fact, many inhibitors of Akt pathway have been identified and clinical studies of some agents are ongoing. In this review, we describe Akt signaling pathway components and its cellular functions as well as the alterations in human cancers and the therapeutic approaches for targeting the Akt pathway in cancer.
Akt（蛋白激酶B）是一种丝氨酸/苏氨酸激酶，是广泛不同的细胞过程（包括增殖、分化、迁移、存活和代谢）的核心调节因子。Akt通过生长因子受体，以磷脂酰肌醇3激酶（PI3K）依赖的方式被多种刺激激活。Akt也受到肿瘤抑制因子10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）的负调控。正常的Akt/PKB/PTEN信号传导的破坏在许多人类癌症中经常发生，这在癌症的发生、发展和治疗抗性中起重要作用。大量研究表明，阻断Akt信号传导会导致肿瘤细胞凋亡和生长抑制。因此，这条包括Akt上下游的信号通路最近作为有效的癌症治疗策略的新靶点引起了相当大的关注。事实上，已经鉴定出许多Akt通路抑制剂，并且一些药物的临床研究正在进行。在这篇综述中，我们描述了Akt信号通路的组成部分及其细胞功能，以及人类癌症中的改变和针对癌症中Akt通路的治疗方法。
