School of Biological Sciences and Institute for Molecular Biology and Genetics, Seoul National University, Seoul 08826, South Korea.
Proteina Co., Ltd., Seoul 08826, South Korea.
Curr Opin Chem Biol. 2019 Dec;53:75-81. doi: 10.1016/j.cbpa.2019.07.001. Epub 2019 Aug 31.
Most cell signaling and surveillance circuits are physically maintained through a dense network of protein-protein interactions (PPIs). Genetic mutations, epigenetic changes as well as alterations in cellular microenvironment can markedly rewire the patterns of PPIs, which leads to neoplastic growth of cancer cells. There are accumulating evidences that drugs that target-specific PPI pairs may provide an opportunity to treat cancers with a higher specificity and efficacy than those inhibiting enzymatic activity of oncogenic proteins. Therefore, identification of driving PPIs in a given cancer not only improves our understanding for individual cancers, but it also provides therapeutic opportunities to cure the specific cancer. In this review, we introduce some examples of aberrant PPI complexes identified in several major types of cancers, and recent technical developments that permit assessment of PPI strength in clinical specimens. Finally, we discuss the potential use of such PPI profiling for the purpose of precision medicine.
大多数细胞信号转导和监控回路是通过蛋白质-蛋白质相互作用（PPIs）的密集网络来维持的。遗传突变、表观遗传变化以及细胞微环境的改变都可以显著改变 PPIs 的模式，从而导致癌细胞的肿瘤生长。越来越多的证据表明，针对特定 PPI 对的药物可能提供了一种机会，可以比抑制致癌蛋白的酶活性更具特异性和疗效地治疗癌症。因此，鉴定特定癌症中的驱动性 PPI 不仅可以提高我们对个体癌症的理解，而且还为治愈特定癌症提供了治疗机会。在这篇综述中，我们介绍了几种主要类型癌症中鉴定出的异常 PPI 复合物的一些例子，以及最近允许评估临床标本中 PPI 强度的技术发展。最后，我们讨论了这种 PPI 分析在精准医学中的潜在用途。
