Glycogen synthase kinase 3beta (GSK3beta) in tumorigenesis and cancer chemotherapy.
Glycogen synthase kinase 3beta (GSK3beta) in tumorigenesis and cancer chemotherapy.
复制标题
DOI：
10.1016/j.canlet.2008.05.045
复制
发表时间：
2009-01-18
期刊：
影响因子：
9.7
通讯作者：
Luo J
中科院分区：
文献类型：
--
作者：
Luo J
糖原合成酶激酶3β(GSK3β)是一种存在于所有真核生物中的多功能丝氨酸/苏氨酸激酶，已被初步确定为胰岛素依赖型糖原合成的关键调节因子。现已知道Gsk3β在多种细胞过程中发挥作用，包括增殖、分化、运动和生存。GSK3β的异常调控与一系列人类疾病有关，包括非胰岛素依赖型糖尿病、心血管疾病、一些神经退行性疾病和双相情感障碍。因此，GSK3β抑制剂的治疗潜力成为一个重要的研究领域。但是，GSK3β也参与了肿瘤的转化和肿瘤的发生。Gsk3β在肿瘤发生和癌症进展中的作用仍然存在争议；它可能对某些类型的肿瘤起到“肿瘤抑制因子”的作用，但对其他类型的肿瘤则促进生长和发育。GSK3β在肿瘤化疗中也参与药物敏感性/耐药性的调节。因此，尽管GSK3β是治疗许多人类疾病的有吸引力的靶点，但它对肿瘤发生和癌症化疗的潜在影响需要仔细评估。这篇简短的综述讨论了GSK3β在肿瘤发生/癌症进展中的作用以及它对癌症化疗的调控。
Glycogen synthase kinase 3β (GSK3β), a multifunctional serine/threonine kinase found in all eukaryotes, had been initially identified as a key regulator of insulin-dependent glycogen synthesis. It is now known that GSK3β functions in diverse cellular processes including proliferation, differentiation, motility and survival. Aberrant regulation of GSK3β has been implicated in a range of human pathologies including non-insulin-dependent diabetes mellitus, cardiovascular disease, some neurodegenerative diseases, and bipolar disorder. As a consequence, the therapeutic potential of GSK3β inhibitors has become an important area of investigation. However, GSK3β also participates in neoplastic transformation and tumor development. The role of GSK3β in tumorigenesis and cancer progression remains controversial; it may function as a “tumor suppressor” for certain types of tumors, but promotes growth and development for some others. GSK3β also mediates drug sensitivity/resistance in cancer chemotherapy. Therefore, although GSK3β is an attractive therapeutic target for a number of human diseases, its potential impact on tumorigenesis and cancer chemotherapy needs to be carefully evaluated. This mini-review discusses the role of GSK3β in tumorigenesis/cancer progression as well as its modulation of cancer chemotherapy.