Cancer Preventive Material Development Research Center, Institute of Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
Ilsong Institute of Life Science, Hallym University, Anyang, Kyonggi-do, Republic of Korea.
Adv Cancer Res. 2013;120:1-38. doi: 10.1016/B978-0-12-401676-7.00001-2.
Since its initial identification as a HIV-1-inducible gene in 2002, astrocyte elevated gene-1 (AEG-1), subsequently cloned as metadherin (MTDH) and lysine-rich CEACAM1 coisolated (LYRIC), has emerged over the past 10 years as an important oncogene providing a valuable prognostic marker in patients with various cancers. Recent studies demonstrate that AEG-1/MTDH/LYRIC is a pleiotropic protein that can localize in the cell membrane, cytoplasm, endoplasmic reticulum (ER), nucleus, and nucleolus, and contributes to diverse signaling pathways such as PI3K-AKT, NF-κB, MAPK, and Wnt. In addition to tumorigenesis, this multifunctional protein is implicated in various physiological and pathological processes including development, neurodegeneration, and inflammation. The present review focuses on the discovery of AEG-1/MTDH/LYRIC and conceptualizes areas of future direction for this intriguing gene. We begin by describing how AEG-1, MTDH, and LYRIC were initially identified by different research groups and then discuss AEG-1 structure, functions, localization, and evolution. We conclude with a discussion of the expression profile of AEG-1/MTDH/LYRIC in the context of cancer, neurological disorders, inflammation, and embryogenesis, and discuss how AEG-1/MTDH/LYRIC is regulated. This introductory discussion of AEG-1/MTDH/LYRIC will serve as the basis for the detailed discussions in other chapters of the unique properties of this intriguing molecule.
自 2002 年首次被鉴定为 HIV-1 诱导基因以来，星形细胞上调基因-1（AEG-1），随后被克隆为富含赖氨酸的 CEACAM1 共分离物（LYRIC），在过去的 10 年中作为一种重要的癌基因出现，为各种癌症患者提供了有价值的预后标志物。最近的研究表明，AEG-1/MTDH/LYRIC 是一种多功能蛋白，可定位于细胞膜、细胞质、内质网（ER）、核和核仁，并参与多种信号通路，如 PI3K-AKT、NF-κB、MAPK 和 Wnt。除了肿瘤发生，这种多功能蛋白还与各种生理和病理过程有关，包括发育、神经退行性变和炎症。本综述重点介绍了 AEG-1/MTDH/LYRIC 的发现，并为这个有趣的基因设想了未来的研究方向。我们首先描述了不同研究小组最初如何鉴定 AEG-1、MTDH 和 LYRIC，然后讨论了 AEG-1 的结构、功能、定位和进化。最后，我们讨论了 AEG-1/MTDH/LYRIC 在癌症、神经退行性疾病、炎症和胚胎发生中的表达谱，并讨论了 AEG-1/MTDH/LYRIC 是如何被调节的。对 AEG-1/MTDH/LYRIC 的介绍性讨论将为该有趣分子的其他章节中对其独特性质的详细讨论提供基础。
