Regulation of the Hippo Pathway by Phosphatidic Acid-Mediated Lipid-Protein Interaction

被引：83

作者：

Han, Han ^{[1
]}

Qi, Ruxi ^{[2
]}

Zhou, Jeff Jiajing ^{[1
]}

Ta, Albert Paul ^{[1
]}

Yang, Bing ^{[1
]}

Nakaoka, Hiroki J. ^{[1
]}

Seo, Gayoung ^{[1
]}

Guan, Kun-Liang ^{[3
,4
]}

Luo, Ray ^{[2
]}

Wang, Wenqi ^{[1
]}

机构：

[1] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA

[2] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA

[3] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA

[4] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA

来源：

MOLECULAR CELL | 2018年 / 72卷 / 02期

关键词：

SKELETAL-MUSCLE HYPERTROPHY; ADP-RIBOSYLATION FACTOR; BOTULINUM C3 EXOENZYME; PHOSPHOLIPASE-D; TUMOR-SUPPRESSOR; LYSOPHOSPHATIDIC ACID; MAMMALIAN TARGET; BINDING PROTEINS; KINASE CASCADE; GROWTH-CONTROL;

D O I：

10.1016/j.molcel.2018.08.038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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.

引用

页码：328 / +

页数：21

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