Department of Central Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China.
Biochem Biophys Res Commun. 2013 Sep 20;439(2):167-72. doi: 10.1016/j.bbrc.2013.08.071. Epub 2013 Aug 28.
Yes-associated protein (YAP), the downstream effector of Hippo signaling pathway as well as c-Myc has been linked to hepatocarcinogenesis. However, little is known about whether and how YAP and c-Myc interacts with each other. In this study, we find YAP-c-Myc interaction is critical for liver cancer cell both in vitro and in vivo. Moreover, both c-Myc and YAP proteins are closely correlated in human liver cancer samples. Mechanistically, YAP promotes c-Myc transcriptional output through c-Abl. By contrast, c-Myc enhances protein expression independent of transcription. Taken together, our study uncovers a novel positive auto-regulatory feedback loop underlying the interaction between YAP and c-Myc in liver cancer, suggesting YAP and c-Myc links Hippo/YAP and c-Myc pathways, and thus may be helpful in the development of effective diagnosis and treatment strategies against liver cancer.
Yes 相关蛋白（YAP）是 Hippo 信号通路的下游效应物，与 c-Myc 相关，已被证实与肝癌的发生有关。然而，目前尚不清楚 YAP 和 c-Myc 是否以及如何相互作用。在本研究中，我们发现 YAP-c-Myc 相互作用对于体外和体内的肝癌细胞都是至关重要的。此外，在人类肝癌样本中，c-Myc 和 YAP 蛋白密切相关。在机制上，YAP 通过 c-Abl 促进 c-Myc 的转录输出。相反，c-Myc 增强蛋白表达而不依赖于转录。总之，我们的研究揭示了肝癌中 YAP 和 c-Myc 相互作用的新的正反馈自动调节环，提示 YAP 和 c-Myc 连接 Hippo/YAP 和 c-Myc 通路，因此可能有助于开发针对肝癌的有效诊断和治疗策略。
