Diverse mechanisms of AKT pathway activation in human malignancy.

Diverse mechanisms of AKT pathway activation in human malignancy.
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DOI:
10.2174/1568009611313030002
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发表时间:
2013-03
影响因子:
3
通讯作者:
Testa JR
Testa JR
中科院分区:
医学4区
文献类型:
--
作者:
Cheung M;Testa JR

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AKT/PKB(蛋白激酶B)是介导受体酪氨酸激酶和磷脂酰肌醇3-激酶信号的中心蛋白。AKT激酶参与许多重要的细胞过程,包括细胞增殖和存活、响应于营养可用性的细胞大小、肿瘤侵袭/转移和血管生成。AKT信号通路的各种组分分别由肿瘤抑制基因和癌基因编码,其丢失或激活在肿瘤发生中起重要作用。越来越多的证据连接失调AKT信号与散发性人类癌症和遗传性癌症易感综合征进行了讨论。我们还强调了关于AKT 1,AKT 2和AKT 3激活突变参与躯体过度生长障碍的新发现:变形综合征,低血糖伴肥大和半侧巨脑畸形。此外,我们回顾了最近的文献,记录了AKT信号通路在人类癌症中被激活的各种方式以及分子靶向治疗的后果。
AKT/PKB (Protein Kinase B) are central proteins mediating signals from receptor tyrosine kinases and phosphatidylinositol 3-kinase. AKT kinases are involved in a number of important cellular processes including cell proliferation and survival, cell size in response to nutrient availability, tumor invasion/metastasis, and angiogenesis. Various components of the AKT signaling pathway are encoded by tumor suppressor genes and oncogenes whose loss or activation, respectively, plays an important role in tumorigenesis. The growing body of evidence connecting deregulated AKT signaling with sporadic human cancers and inherited cancer predisposition syndromes is discussed. We also highlight new findings regarding the involvement of activating mutations of AKT1, AKT2, and AKT3 in somatic overgrowth disorders: Proteus syndrome, hypoglycemia with hypertrophy, and hemimegalencephaly, respectively. In addition, we review recent literature documenting the various ways the AKT signaling pathway is activated in human cancers and consequences for molecularly targeted therapies.
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