Molecular Cancer Research, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
Cold Spring Harb Perspect Med. 2018 Feb 1;8(2):a031468. doi: 10.1101/cshperspect.a031468.
Our laboratory has studied Ras and Ras-like proteins since the discovery of the Ras oncogene 35 years ago. In this review, I will give an account of what we have done in these 35 years and indicate the main papers that have guided our research. Our efforts started with the early analysis of mutant Ras in human tumors followed by deciphering of the role of Ras in signal transduction pathways. In an attempt to interfere in Ras signaling we turned to Rap proteins. These proteins are the closest relatives of Ras and were initially identified as Ras antagonists. However, our studies revealed that the Rap signaling network primarily is involved in spatiotemporal control of cell adhesion, in part through regulation of the actin cytoskeleton. More recently we returned to Ras, trying to interfere in Ras signaling by combinatorial drug testing using the organoid technology.
我们实验室自 35 年前发现 Ras 癌基因以来，一直在研究 Ras 和 Ras 样蛋白。在这篇综述中，我将介绍我们在这 35 年里所做的工作，并指出指导我们研究的主要论文。我们的工作始于对人类肿瘤中突变 Ras 的早期分析，随后是对 Ras 在信号转导途径中的作用的解码。为了尝试干扰 Ras 信号，我们转向 Rap 蛋白。这些蛋白质是 Ras 的近亲，最初被鉴定为 Ras 拮抗剂。然而，我们的研究表明，Rap 信号网络主要参与细胞黏附的时空控制，部分通过调节肌动蛋白细胞骨架。最近，我们又回到了 Ras，试图通过使用类器官技术进行组合药物测试来干扰 Ras 信号。
