PI3K 和 STAT3：新的联盟。
PI3K and STAT3: a new alliance.
机构信息
The Scripps Research Institute, Department of Molecular and Experimental Medicine, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
出版信息
Cancer Discov. 2011 Nov;1(6):481-6. doi: 10.1158/2159-8290.CD-11-0218.
Abstract
UNLABELLED
Recent proteomic data have uncovered an interdependence of PI3K and STAT3. In PI3K-tranformed murine cells, STAT3 is phosphorylated on Y705 and activated in a PI3K-dependent manner. Dominant negative STAT3 interferes with PI3K-induced oncogenic transformation. Phosphorylation of STAT3 in PI3K-transformed murine cells is mediated by the TEC kinase BMX. Observations on glioblastoma stem cells reveal similar critical roles for STAT3 and BMX. The new data document an important role of STAT3 in PI3K-driven oncogenic transformation and mark BMX as a promising therapeutic target that could enhance the effectiveness of PI3K inhibitors.
SIGNIFICANCE
The PI3K–TOR and STAT3 signaling pathways represent two distinct regulatory networks. The discovery of a functional link between these pathways is significant for our understanding of PI3K- and STAT3-driven oncogenic mechanisms and identifies the TEC kinase BMX as a new cancer target.
摘要
未标记
最近的蛋白质组学数据揭示了 PI3K 和 STAT3 的相互依存关系。在 PI3K 转化的鼠细胞中，STAT3 在 Y705 上被磷酸化，并以 PI3K 依赖性方式被激活。显性负 STAT3 干扰 PI3K 诱导的致癌转化。PI3K 转化的鼠细胞中 STAT3 的磷酸化由 TEC 激酶 BMX 介导。对神经胶质瘤干细胞的观察揭示了 STAT3 和 BMX 类似的关键作用。新数据记录了 STAT3 在 PI3K 驱动的致癌转化中的重要作用，并将 BMX 标记为一种有前途的治疗靶点，可增强 PI3K 抑制剂的有效性。
意义
PI3K–TOR 和 STAT3 信号通路代表两个不同的调节网络。发现这些通路之间的功能联系对于我们理解 PI3K 和 STAT3 驱动的致癌机制具有重要意义，并将 TEC 激酶 BMX 鉴定为新的癌症靶点。
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