Sixian Qi, Zhenxing Zhong, Yuwen Zhu, Yebin Wang, Mingyue Ma, Yu Wang, Xincheng Liu, Ruxin Jin, Zhihan Jiao, Rui Zhu, Zhao Sha, Kyvan Dang, Ying Liu, Dae-Sik Lim, Junhao Mao, Lei Zhang, Fa-Xing Yu
The Hippo pathway is a central regulator of organ size and tumorigenesis and is commonly depicted as a kinase cascade, with an increasing number of regulatory and adaptor proteins linked to its regulation over recent years. Here, we propose that two Hippo signaling modules, MST1/2-SAV1-WWC1-3 (HPO1) and MAP4K1-7-NF2 (HPO2), together regulate the activity of LATS1/2 kinases and YAP/TAZ transcriptional co-activators. In mouse livers, the genetic inactivation of either HPO1 or HPO2 module results in partial activation of YAP/TAZ, bile duct hyperplasia, and hepatocellular carcinoma (HCC)...
March 15, 2023: EMBO Journal