Jia Weijuan, Feng Y I, Sanders Andrew J, Davies Eleri L, Jiang Wen G
Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff University, Cardiff, U.K. Breast Cancer Department, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, P.R. China.
Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff University, Cardiff, U.K.
Anticancer Res. 2016 Mar;36(3):1103-9.
Phosphoinositide 3-kinase enhancer (PIKE) belongs to a family of GTP-binding proteins, including three isoforms, PIKE-S, PIKE-L and PIKE-A. PIKE-S and PIKE-L interact with PI3K to enhance the activity of PI3K, but PIKE-A directly binds to AKT and up-regulates its activity. PIKEs also interacts with a variety of signaling molecules in addition to PI3K and AKT, to trigger multiple physiological functions. Overexpression or mutation of PIKE has been observed in a variety of tumors, especially PIKE-A, which acts as a proto-oncogene, promoting cancer cell growth, transformation and invasion through AKT signaling. Knockdown of PIKE-A or blocking of PIKE-A/AKT interactions enhances apoptosis, inhibits cancer cell proliferation, migration and invasion. Moreover, PIKE plays an important role in tumorigenesis through other signaling pathways, such as focal adhesion kinase, signal transducer and activator of transcription 5A, and nuclear factor kappa-light-chain-enhancer of activated B cells. The current review explores the functional role of PIKE and its potential in cancer therapy.
磷酸肌醇3激酶增强子（PIKE）属于GTP结合蛋白家族，包括三种亚型，即PIKE-S、PIKE-L和PIKE-A。PIKE-S和PIKE-L与PI3K相互作用以增强PI3K的活性，但PIKE-A直接与AKT结合并上调其活性。除了PI3K和AKT外，PIKE还与多种信号分子相互作用，以触发多种生理功能。在多种肿瘤中已观察到PIKE的过表达或突变，尤其是PIKE-A，它作为一种原癌基因，通过AKT信号促进癌细胞生长、转化和侵袭。敲低PIKE-A或阻断PIKE-A/AKT相互作用可增强细胞凋亡，抑制癌细胞增殖、迁移和侵袭。此外，PIKE通过其他信号通路在肿瘤发生中起重要作用，如粘着斑激酶、信号转导和转录激活因子5A以及活化B细胞核因子κB轻链增强子。本综述探讨了PIKE的功能作用及其在癌症治疗中的潜力。
