Student Research Committee, Babol University of Medical Sciences, Babol, Iran; Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; North Research Center, Pasteur Institute, Amol, Iran.
Department of Genetics, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran.
Life Sci. 2020 Dec 1;262:118513. doi: 10.1016/j.lfs.2020.118513. Epub 2020 Oct 1.
PI3K/AKT/mTOR pathway is one of the most important signaling pathways involved in normal cellular processes. Its aberrant activation modulates autophagy, epithelial-mesenchymal transition, apoptosis, chemoresistance, and metastasis in many human cancers. Emerging evidence demonstrates that some infections as well as epigenetic regulatory mechanisms can control PI3K/AKT/mTOR signaling pathway. In this review, we focused on the role of this pathway in gastric cancer development, prognosis, and metastasis, with an emphasis on epigenetic alterations including DNA methylation, histone modifications, and post-transcriptional modulations through non-coding RNAs fluctuations as well as H. pylori and Epstein-Barr virus infections. Finally, we reviewed different molecular targets and therapeutic agents in clinical trials as a potential strategy for gastric cancer treatment through the PI3K/AKT/mTOR pathway.
PI3K/AKT/mTOR 通路是参与正常细胞过程的最重要信号通路之一。其异常激活调节许多人类癌症中的自噬、上皮-间充质转化、细胞凋亡、化学耐药性和转移。新出现的证据表明，一些感染以及表观遗传调控机制可以控制 PI3K/AKT/mTOR 信号通路。在这篇综述中，我们重点关注该通路在胃癌发展、预后和转移中的作用，并强调表观遗传改变，包括通过非编码 RNA 波动以及 H. pylori 和 Epstein-Barr 病毒感染的 DNA 甲基化、组蛋白修饰和转录后修饰。最后，我们回顾了临床试验中不同的分子靶点和治疗药物，作为通过 PI3K/AKT/mTOR 通路治疗胃癌的潜在策略。
