The hippo tumor suppressor network: from organ size control to stem cells and cancer.
The hippo tumor suppressor network: from organ size control to stem cells and cancer.
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DOI：
10.1158/0008-5472.can-13-2392
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发表时间：
2013-11-01
期刊：
影响因子：
11.2
通讯作者：
Camargo FD
中科院分区：
文献类型：
--
作者：
Halder G;Camargo FD
今年5月在加州的蒙特雷举行了关于“河马”途径的第三次会议，作为一次基石专题讨论会。在过去的几年里，Hippo肿瘤抑制通路已经成为一个复杂的信号网络，对我们理解癌症，发育和干细胞生物学的分子机制具有重要意义。第1-3段）。这一通路的主要效应物是Yes相关蛋白（雅普）和具有PDZ结合基序的转录辅激活因子（TAZ），它们是作为干细胞稳态和强致癌基因的调节剂的转录辅激活因子。Hippo途径组分，特别是雅普和TAZ的异常表达经常在人类癌症中观察到，并且具有激活雅普和TAZ或直接过表达雅普的突变的小鼠在多种组织中发展癌症。因此，Hippo通路已成为开发抗癌药物的有吸引力的靶点。然而，许多关于Hippo通路的问题仍然没有答案，近年来出现了一些关于该通路功能的悖论。例如，雅普是作为癌基因还是肿瘤抑制基因，调节该途径活性的机制是什么？今年的Hippo会议上提出了一系列新发现，反映了Hippo途径的各个方面，从信号转导机制到癌症研究和再生。因此，本次会议见证了这一领域的快速进展，这在很大程度上要归功于果蝇遗传学家、哺乳动物信号分子以及癌症和发育生物学家之间的积极对话。尽管近年来Hippo通路的许多上游成分已经被鉴定，但对信号转导机制以及不同输入如何整合到通路中的了解还很有限。在过去的两年里，这一领域取得了实质性的进展，一些研究人员提出了新的发现的信号转导机制。Kun-Liang Guan（加州大学圣地亚哥分校，拉霍亚，CA）发表了第一个主题演讲，并表明Hippo通路受G-
The third meeting on the Hippo pathway was held as a Keystone Symposia Conference last May in Monterrey, California. Over the past several years, the Hippo tumor suppressor pathway has emerged as a complex signaling network that has significant implications for our understanding of the molecular mechanisms of cancer, development, and stem cell biology (reviewed in refs. 1–3). The main effectors of this pathway, Yes-associated protein (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ), are transcriptional coactivators that act as regulators of stem cell homeostasis and potent oncogenes. Abnormal expression of Hippo pathway components, in particular YAP and TAZ, is often observed in human cancer, and mice with mutations that activate YAP and TAZ or that directly overexpress YAP develop cancer in a variety of tissues. Therefore, the Hippo pathway has become an attractive target for the development of anticancer drugs. However, many questions about the Hippo pathway are still unanswered and several paradoxes about the function of the pathway have emerged in recent years. For example, does YAP act as an oncogene or a tumor suppressor, and what are the mechanisms that regulate the activity of the pathway? A flurry of new discoveries was presented at this year's Hippo meeting, which reflected on all aspects of the Hippo pathway, from signal transduction mechanisms to cancer research and regeneration. Thus, the meeting witnessed the fast progress in this field, which is due, in large part, to an active dialog between Drosophila geneticists, mammalian signalers, and cancer and developmental biologists.Although many upstream components of the Hippo pathway have been identified in recent years, mechanisms of signal transduction and how different inputs are integrated into the pathway have been poorly understood. Substantial progress has been made in this area in the past 2 years and several researchers presented new findings of signal transduction mechanisms. Kun-Liang Guan (University of California, San Diego, La Jolla, CA) presented the first keynote lecture and showed that the Hippo pathway is acutely regulated by G-