PI3K/AKT Pathway and the Epithelial-Mesenchymal Transition
PI3K/AKT Pathway and the Epithelial-Mesenchymal Transition
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DOI：
10.1007/978-1-4419-0711-0_2
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发表时间：
2010-01-01
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影响因子：
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通讯作者：
Larue, L.
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文献类型：
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作者：
Bellacosa, A.;Larue, L.
磷脂酰肌醇3-激酶催化亚单位(PIK3；EC 2.7.1.137)是人类肿瘤中最常见的突变基因之一，其抑制因子PTEN也是如此。据估计，PIK3CA在32%的结直肠癌、36%的肝细胞癌、36%的子宫内膜癌、25%的乳腺癌、15%的间变性少突胶质瘤以及5%的髓母细胞瘤和间变性星形细胞瘤中携带功能获得突变(最近在Velculescu，2008年进行了综述)。同样，在50%的子宫内膜癌、30%的胶质母细胞瘤、10%的前列腺癌和5%的乳腺癌中发现了PTEN的自发突变。此外，PTEN的遗传突变会导致多种疾病，如考登综合征，这与癌症风险增加有关(最近在Kenry和Parsons，2008年回顾)。此外，在几乎所有研究的肿瘤类型中都描述了AKT激酶的频繁改变和过度激活(在Bellacosa等人，2005年；Brugge等人，2007年)中进行了综述。虽然AKT通路的许多下游效应分子参与了细胞自主过程(即细胞周期和细胞凋亡)，但下一章将集中讨论AKT信号在上皮-间充质转化中的意义，特别是在子宫内膜癌中的PI3K-AKT-NF-κB-Snail通路，重点是E-钙粘素的调节。
The catalytic subunit of the phosphatidylinositol 3-kinase (PIK3; EC 2.7.1.137) is one of the most frequently mutated gene in human cancers, as is its inhibitorPTEN. By some estimates,PIK3CAcarries gain-of-function mutations in 32% of colorectal cancers, 36% of hepatocellular carcinomas, 36% of endometrial carcinomas, 25% of breast carcinomas, 15% of anaplastic oligodendrogliomas, and 5% of medulloblastomas and anaplastic astrocytomas (recently reviewed in Velculescu, 2008). Similarly, spontaneous mutations inPTENare found in 50% of endometrial cancers, 30% of glioblastomas, 10% of prostate, and 5% of breast carcinomas. Moreover, inherited mutations inPTENlead to a variety of conditions, such as Cowden syndrome, which are associated with an increased risk of cancer (recently reviewed in Keniry and Parsons, 2008). In addition, frequent alterations and hyperactivation of AKT kinases have been described in almost every tumor type studied (reviewed in Bellacosa et al., 2005; Brugge et al., 2007). While many of the downstream effectors of the AKT pathway are involved in cell autonomous processes (i.e., cell cycle and apoptosis), the following chapter will focus on the implications of aberrant AKT signaling for epithelial–mesenchymal transition, in particular on the PI3K–AKT–NF-κB–Snail pathways in EMT with emphasis on E-cadherin regulation.