比利时鲁汶大学Georg Halder研究组发现，Hippo通路中的效应蛋白YAP和TAZ在肿瘤周围的激活能够抑制小鼠肝癌。这一研究成果于2019年11月22日发表在国际学术期刊《科学》上。
利用小鼠模型，研究人员表明YAP和TAZ也可以发挥肿瘤抑制功能。研究人员发现肝脏肿瘤周围的正常肝细胞显示出YAP和TAZ的激活，而这些肿瘤周围肝细胞中Yap和Taz的缺失加速了肿瘤的生长。相反，肿瘤周围肝细胞中YAP的实验性过度激活触发了原发性肝肿瘤和黑色素瘤来源的肝转移的减少。
此外，尽管在野生型肝脏中生长的肿瘤细胞需要YAP和TAZ才能存活，但被Yap和Taz缺陷型肝细胞围绕的肿瘤细胞却并不依赖YAP和TAZ。因此，肿瘤细胞的存活取决于肿瘤细胞及其周围组织中YAP和TAZ的相对活性，这表明YAP和TAZ通过细胞竞争机制消除肿瘤细胞从而发挥作用。
据介绍，在肿瘤生长的实验模型中，Hippo信号通路及其两个下游效应蛋白，即YAP和TAZ转录共激活因子，是肿瘤生长的驱动因素。
附：英文原文
Title: Peritumoral activation of the Hippo pathway effectors YAP and TAZ suppresses liver cancer in mice
Author: Iván M. Moya, Stéphanie A. Castaldo, Laura Van den Mooter, Soheil Soheily, Leticia Sansores-Garcia, Jelle Jacobs, Inge Mannaerts, Jun Xie, Elisabeth Verboven, Hanne Hillen, Ana Algueró-Nadal, Ruchan Karaman, Matthias Van Haele, Weronika Kowalczyk, Maxime De Waegeneer, Stefaan Verhulst, Panagiotis Karras, Leen van Huffel, Lars Zender, Jean-Christophe Marine, Tania Roskams, Randy Johnson, Stein Aerts, Leo A. van Grunsven, Georg Halder
Issue&Volume: 2019/11/22
Abstract: The Hippo signaling pathway and its two downstream effectors, the YAP and TAZ transcriptional coactivators, are drivers of tumor growth in experimental models. Studying mouse models, we show that YAP and TAZ can also exert a tumor-suppressive function. We found that normal hepatocytes surrounding liver tumors displayed activation of YAP and TAZ and that deletion of Yap and Taz in these peritumoral hepatocytes accelerated tumor growth. Conversely, experimental hyperactivation of YAP in peritumoral hepatocytes triggered regression of primary liver tumors and melanoma-derived liver metastases. Furthermore, whereas tumor cells growing in wild-type livers required YAP and TAZ for their survival, those surrounded by Yap- and Taz-deficient hepatocytes were not dependent on YAP and TAZ. Tumor cell survival thus depends on the relative activity of YAP and TAZ in tumor cells and their surrounding tissue, suggesting that YAP and TAZ act through a mechanism of cell competition to eliminate tumor cells.
DOI: 10.1126/science.aaw9886
Source: https://science.sciencemag.org/content/366/6468/1029