Hippo通路在控制器官大小和肿瘤的发生中起着关键作用，成为近年来一大研究热点。作为Hippo通路核心元件的YAP/TAZ在很多肿瘤中高表达并参与肿瘤的的发生发展，但目前对其上游胞膜上的激活分子知之甚少。CD44作为一个跨膜受体，参与多种重要的生理病理过程，是多种肿瘤干细胞的重要分子标志。我们的前期工作显示RhoA是CD44与YAP之间重要的信号传递分子之一，但CD44对Hippo通路的具体调控机制还不清楚，亟待解决。项目组在前期研究中亦发现两者之间联系的其它重要线索。本课题拟从CD44是如何通过胞浆中的其它重要信号分子来调控YAP/TAZ的活性、稳定性及其在细胞内的亚定位；细胞核内CD44与YAP/TAZ间的相互作用等方面深入探讨CD44 对Hippo通路的具体调控机制。该项目对阐明CD44和YAP/TAZ在肿瘤发生发展中的作用、为其作为肿瘤分子靶向治疗的新靶点提供重要的理论依据。

Abstract：The Hippo pathway, a study focus in recent years, plays a key role in the control of organ size and carcinogenesis. YAP/TAZ, the core components of the Hippo pathway, highly express in many tumors and deeply involved in cancer occurrence and development. But the upstream activating molecules on the cell membrane of this pathway have rarely been studied. CD44, a trans-membrane receptor, participates in many important physiological and pathological processes, and is an important molecular marker in many cancer stem cells. Our previous work showed that RhoA is an important signaling molecule between CD44 and YAP. But the detail mechanisms for CD44 in regulating Hippo pathway remain unclear. Some important clues between the two molecules have been found in our previous study. This project plans to study how other signaling molecules mediated the regulation of the activity, stability and sub-cellular locolization of YAP / TAZ through CD44. The interaction of CD44 and YAP / TAZ in nucleus will also be explored. This study is trying to elucidate the role of CD44 and YAP/TAZ in carcinogenesis and to provide important evidence for the new targets in cancer molecular targeted therapy.