Chen Ying, Huang Lan, Dong Yongjian, Tao Changli, Zhang Rongxin, Shao Hongwei, Shen Han
Guangdong Province Key Laboratory for Biotechnology Drug Candidates, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
Front Cell Dev Biol. 2020 Oct 6;8:573599. doi: 10.3389/fcell.2020.573599. eCollection 2020.
The substitution of the seventeenth amino acid glutamate by lysine in the homologous structural domain of the Akt1 gene pleckstrin is a somatic cellular mutation found in breast, colorectal, and ovarian cancers, named p. Glu17Lys or E17K. In recent years, a growing number of studies have suggested that this mutation may play a unique role in the development of tumors. In this review article, we describe how AKT1(E17K) mutations stimulate downstream signals that cause cells to emerge transformed; we explore the differential regulation and function of E17K in different physiological and pathological settings; and we also describe the phenomenon that E17K impedes tumor growth by interfering with growth-promoting and chemotherapy-resistant AKT1QCC generation, an intriguing finding that mutants may prolong tumor patient survival by activating feedback mechanisms and disrupting transcription. This review is intended to provide a better understanding of the role of AKT1(E17K) in cancer and to inform the development of AKT1(E17K)-based antitumor strategies.
Akt1基因普列克底物蛋白同源结构域中第17位氨基酸谷氨酸被赖氨酸取代，这是一种在乳腺癌、结直肠癌和卵巢癌中发现的体细胞突变，命名为p.Glu17Lys或E17K。近年来，越来越多的研究表明，这种突变可能在肿瘤发生发展中发挥独特作用。在这篇综述文章中，我们描述了AKT1（E17K）突变如何刺激下游信号导致细胞发生转化；我们探讨了E17K在不同生理和病理环境中的差异调节和功能；我们还描述了E17K通过干扰促进生长和化疗耐药的AKT1QCC生成来阻碍肿瘤生长的现象，这一有趣的发现表明突变体可能通过激活反馈机制和破坏转录来延长肿瘤患者的生存期。这篇综述旨在更好地理解AKT1（E17K）在癌症中的作用，并为基于AKT1（E17K）的抗肿瘤策略的开发提供信息。
