PI3K/PTEN signaling in angiogenesis and tumorigenesis.
PI3K/PTEN signaling in angiogenesis and tumorigenesis.
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DOI：
10.1016/s0065-230x(09)02002-8
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发表时间：
2009
影响因子：
--
通讯作者：
Liu, Ling-Zhi
中科院分区：
文献类型：
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作者：
Jiang, Bing-Hua;Liu, Ling-Zhi
磷脂酰肌醇3-激酶（PI 3 K）和10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）信号通路在多种细胞功能如细胞代谢、增殖、细胞周期进展和存活中起重要作用。PI 3 K被生长因子和血管生成诱导剂如血管内皮生长因子（VEGF）和血管生成素激活。PI 3 K的扩增、突变和抑癌基因PTEN的缺失在各种实体瘤中普遍存在。PI 3 K信号传导分子的上游和下游的遗传改变，例如受体酪氨酸激酶和AKT，分别在人类癌症中也经常改变。PI 3 K信号通过激活AKT和其他靶点以及诱导HIF-1和VEGF表达来调节肿瘤生长和血管生成。血管生成是肿瘤生长和转移所必需的。本文就PI 3 K和PTEN在肿瘤发生和血管生成中的作用和机制，以及PI 3 K下游靶点在信号传递中的作用作一综述。我们还讨论了这些信号分子的串扰和肿瘤生长，转移和肿瘤血管生成过程中的细胞事件。最后，我们总结了PI 3 K，AKT和mTOR抑制剂的潜在应用及其在癌症治疗临床试验中的结果。
Phosphatidylinositol 3-kinase (PI3K) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signaling pathway play an important role in multiple cellular functions such as cell metabolism, proliferation, cell-cycle progression, and survival. PI3K is activated by growth factors and angiogenesis inducers such as vascular endothelial growth factor (VEGF) and angiopoietins. The amplification and mutations of PI3K and the loss of the tumor suppressor PTEN are common in various kinds of human solid tumors. The genetic alterations of upstream and downstream of PI3K signaling molecules such as receptor tyrosine kinases and AKT, respectively, are also frequently altered in human cancer. PI3K signaling regulates tumor growth and angiogenesis by activating AKT and other targets, and by inducing HIF-1 and VEGF expression. Angiogenesis is required for tumor growth and metastasis. In this review, we highlight the recent studies on the roles and mechanisms of PI3K and PTEN in regulating tumorigenesis and angiogenesis, and the roles of the downstream targets of PI3K for transmitting the signals. We also discuss the crosstalk of these signaling molecules and cellular events during tumor growth, metastasis, and tumor angiogenesis. Finally, we summarize the potential applications of PI3K, AKT, and mTOR inhibitors and their outcome in clinical trials for cancer treatment.