河马信号通路
磷脂酸
磷脂酶D
生物
细胞生物学
调节器
信号转导
PLD2型
癌症研究
生物化学
膜
磷脂
基因
作者
Han Han,Ruxi Qi,Jeff Jiajing Zhou,Albert Ta,Bing Yang,Hiroki J. Nakaoka,Gayoung Seo,Kun‐Liang Guan,Ray Luo,Wenqi Wang
出处
期刊:Molecular Cell
[Elsevier]
日期:2018-10-01
卷期号:72 (2): 328-340.e8
被引量:77
标识
DOI:10.1016/j.molcel.2018.08.038
摘要
The Hippo pathway plays a crucial role in organ size control and tumor suppression, but its precise regulation is not fully understood. In this study, we discovered that phosphatidic acid (PA)-related lipid signaling is a key regulator of the Hippo pathway. Supplementing PA in various Hippo-activating conditions activates YAP. This PA-related lipid signaling is involved in Rho-mediated YAP activation. Mechanistically, PA directly interacts with Hippo components LATS and NF2 to disrupt LATS-MOB1 complex formation and NF2-mediated LATS membrane translocation and activation, respectively. Inhibition of phospholipase D (PLD)-dependent PA production suppresses YAP oncogenic activities. PLD1 is highly expressed in breast cancer and positively correlates with YAP activation, suggesting their pathological relevance in breast cancer development. Taken together, our study not only reveals a role of PLD-PA lipid signaling in regulating the Hippo pathway but also indicates that the PLD-PA-YAP axis is a potential therapeutic target for cancer treatment.
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