Targeting GSK-3: a promising approach for cancer therapy?
Targeting GSK-3: a promising approach for cancer therapy?
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DOI：
10.2217/14796694.2.1.91
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发表时间：
2006-02-01
期刊：
影响因子：
--
通讯作者：
Billadeau, Daniel D
中科院分区：
文献类型：
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作者：
Ougolkov, Andrei V;Billadeau, Daniel D
糖原合成酶激酶（GSK）-3已成为治疗多种神经系统疾病（包括阿尔茨海默病、中风和双相情感障碍以及非胰岛素依赖型糖尿病和炎症）的最有吸引力的治疗靶标之一。尽管GSK-3在腺瘤性结肠息肉病（APC）-β-连环蛋白破坏复合物中的突出作用意味着GSK-3的抑制可能通过激活β-连环蛋白导致肿瘤促进，但最近的几项研究揭示了GSK-3在癌症中的活性，并提供了对其调节肿瘤细胞增殖和多种人类恶性肿瘤存活的分子机制的深入了解。事实上，GSK-3 β是核因子（NF）kappaB核活性的关键调节因子，这表明GSK-3 β的抑制可有效治疗具有组成性活性NF kappaB的各种肿瘤。在本文中，作者将讨论目前对GSK-3在人类癌症中的作用及其作为治疗靶点的潜力的理解。
Glycogen synthase kinase (GSK)-3 has emerged as one of the most attractive therapeutic targets for the treatment of multiple neurological diseases, including Alzheimer's, stroke and bipolar disorders, as well as noninsulin-dependent diabetes mellitus and inflammation. Although the prominent role of GSK-3 in the adenomatous polyposis coli (APC)-beta-catenin destruction complex implies that inhibition of GSK-3 could possibly lead to tumor promotion through the activation of beta-catenin, several recent studies have shed new light on the activity of GSK-3 in cancer and provide insight into the molecular mechanisms by which it regulates tumor cell proliferation and survival of multiple human malignancies. In fact, GSK-3beta is a critical regulator of nuclear factor (NF)kappaB nuclear activity, suggesting that inhibition of GSK-3beta could be effective in the treatment of a wide variety of tumors with constitutively active NFkappaB. Herein, the authors will discuss the current understanding of the role of GSK-3 in human cancer and its potential as a therapeutic target.