Pivotal roles of glycogen synthase-3 in hepatocellular carcinoma
Pivotal roles of glycogen synthase-3 in hepatocellular carcinoma
复制标题
DOI：
10.1016/j.jbior.2017.06.002
复制
发表时间：
2017-01-01
影响因子：
--
通讯作者：
Montalto, Giuseppe
中科院分区：
文献类型：
--
作者：
Cervello, Melchiorre;Augello, Giuseppa;Montalto, Giuseppe
肝细胞癌是世界上最常见的癌症之一，是世界上第二常见的癌症和第三常见的癌症死亡原因。在晚期，肝细胞癌是一种高度侵袭性的肿瘤，预后很差，对常规治疗的反应非常有限。因此，仍然需要新的有效和耐受性良好的治疗策略。分子靶向治疗为肝癌的治疗带来了希望。一个有希望的分子靶点是多功能丝氨酸/苏氨酸激酶糖原合成酶激酶3(GSK-3)。GSK-3β在肝细胞癌中的作用仍然存在争议，一些研究表明GSK-3(3)可能作为肿瘤抑制基因在肝细胞癌中发挥作用，而其他研究表明GSK-3β是治疗肝细胞癌的潜在靶点。本文就GSK-3在肝细胞癌中的不同作用及其与胰岛素样生长因子(IGF)、Notch、Wnt/β-catenin、Hedgehog(HH)、转化生长因子-β(TGF-β)等信号通路的相互作用作一综述。此外，还将讨论GSK3在上皮间充质转化(EMT)、侵袭和转移中的关键作用。(C)2017爱思唯尔有限公司。保留所有权利。
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world, and represents the second most frequently cancer and third most common cause of death from cancer worldwide. At advanced stage, HCC is a highly aggressive tumor with a poor prognosis and with very limited response to common therapies. Therefore, there is still the need for new effective and well-tolerated therapeutic strategies. Molecular-targeted therapies hold promise for HCC treatment. One promising molecular target is the multifunctional serine/threonine kinase glycogen synthase kinase 3 (GSK-3). The roles of GSK-3 beta in HCC remain controversial, several studies suggested a possible role of GSK-3 (3 as a tumor suppressor gene in HCC, whereas, other studies indicate that GSK-3 beta is a potential therapeutic target for this neoplasia. In this review, we will focus on the different roles that GSK-3 plays in HCC and its interaction with signaling pathways implicated in the pathogenesis of HCC, such as Insulin-like Growth Factor (IGF), Notch, Wnt/beta-catenin, Hedgehog (HH), and TGF-beta pathways. In addition, the pivotal roles of GSK3 in epithelialmesenchymal transition (EMT), invasion and metastasis will be also discussed. (C) 2017 Elsevier Ltd. All rights reserved.