美国加州大学圣地亚哥分校管坤良教授研究小组最新发现Hippo-YAP通路是联系器官大小调节与癌症的分子信号通路系统。
Hippo信号转导通路是几年前发现的一个信号转导通路。研究发现Hippo信号通路是参与调控器官大小发育的关键信号通路，这一观点首先在果蝇中被发现，后来的研究发现在哺乳动物的发育过程中Hippo有相同的功能。06年Cell发表的一篇文章证实Hippo是一种细胞分裂和死亡的控制开关。Hippo信号转导通路通过促进细胞调亡和限制细胞增殖调控器官大小的发育，越来越多的证据表明，Hippo信号的调控可能与人类的肿瘤发生密切相关。
最新研究发现，在Hippo的下游存在一种转录激活子Yki/YAP/TAZ。在哺乳动物细胞中，Hippo pathway kinase cascade（Hippo通路级联激酶）通过磷酸化和促进细胞质转位来抑制YAP及其同系物TAZ的功能。TEAD家族转录因子是进化上保守的影响YAP生物功能的关键因子。
Yap是一个候选的致癌基因，而Hippo通路上的其他几个因子是肿瘤抑制因子。如果Hippo通路功能失调将导致癌细胞丧失接触性抑制（癌细胞不受接触性抑制局限将更容易扩散，肿瘤灶将更快地扩散）。
因此，Hippo-YAP通路是控制器官大小发育与肿瘤发生的一个信号转导通路。（生物谷Bioon.com）
生物谷专访管坤良教授
生物谷推荐原始出处：
Current Opinion in Cell Biology Volume 20, Issue 6, December 2008,doi:10.1016/j.ceb.2008.10.001
The Hippo–YAP pathway: new connections between regulation of organ size and cancer
Bin Zhao1, 2, Qun-Ying Lei3, and Kun-Liang Guan1,
1Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093-0815, USA
2Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
3Department of Biological Chemistry, School of Medicine, and Molecular and Cellular Biology Laboratory, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
The control of organ size is a basic biological question. In the past several years, the Hippo signaling pathway has been delineated and shown to be crucial in control of organ size in both Drosophila and mammals. Acting downstream of the Hippo pathway is the Yki/YAP/TAZ transcription co-activators. In mammalian cells, the Hippo pathway kinase cascade inhibits YAP and its paralog TAZ by phosphorylation and promotion of their cytoplasmic localization. The TEAD family transcription factors have recently been identified as evolutionarily conserved key mediators of YAP biological functions. yap is a candidate oncogene, and several other components of the Hippo pathway are tumor suppressors. Dysregulation of the Hippo pathway contributes to the loss of contact inhibition observed in cancer cells. Therefore, the Hippo–YAP pathway connects the regulation of organ size and tumorigenesis.
