The dysregulation of phosphatidylinositol 3-kinase (PI3K) signaling plays a pivotal role in driving neoplastic transformation by promoting uncontrolled cell survival and proliferation. This oncogenic activity is primarily caused by mutations that are frequently found in PI3K genes and constitutively activate the PI3K signaling pathway. However, tumorigenesis can also arise from nonmutated PI3K proteins adopting unique active conformations, further complicating the understanding of PI3K-driven cancers. Recent structural studies have illuminated the functional divergence among highly homologous PI3K proteins, revealing how subtle structural alterations significantly impact their activity and contribute to tumorigenesis. In this review, we summarize current knowledge of Class I PI3K proteins and aim to unravel the complex mechanism underlying their oncogenic traits. These insights will not only enhance our understanding of PI3K-mediated oncogenesis but also pave the way for the design of novel PI3K-based therapies to combat cancers driven by this signaling pathway.
磷脂酰肌醇3-激酶（PI3K）信号通路的失调通过促进细胞不受控制的存活与增殖，在驱动肿瘤转化过程中发挥着关键作用。这种致癌活性主要源于PI3K基因中频繁出现的突变，这些突变会导致PI3K信号通路持续激活。然而，肿瘤发生也可能源于未发生突变的PI3K蛋白通过形成独特的活性构象而引发，这进一步增加了对PI3K驱动型癌症的理解难度。近期结构研究揭示了高度同源的PI3K蛋白之间的功能差异，阐明了细微的结构改变如何显著影响其活性并促进肿瘤发生。本综述总结了当前对I类PI3K蛋白的认知，旨在揭示其致癌特性的复杂机制。这些见解不仅将深化我们对PI3K介导的肿瘤发生机制的理解，还将为设计基于PI3K的新型抗癌疗法铺平道路。
肿瘤(癌症)患者之家