Document Type
Article
Journal Title
Oncotarget
Publication Date
Winter 11-3-2015
Volume
6
Abstract
The transcriptional co-activator Yes-associated protein, YAP, is a main effector in the Hippo tumor suppressor pathway. We recently defined a mechanism for positive regulation of YAP through CDK1-mediated mitotic phosphorylation. Here, we show that active YAP promotes pancreatic cancer cell migration, invasion and anchorage-independent growth in a mitotic phosphorylation-dependent manner. Mitotic phosphorylation is essential for YAP-driven tumorigenesis in animals. YAP reduction significantly impairs cell migration and invasion. Immunohistochemistry shows significant upregulation and nuclear localization of YAP in metastases when compared with primary tumors and normal tissue in human. Mitotic phosphorylation of YAP controls a unique transcriptional program in pancreatic cells. Expression profiles reveal LPAR3 (lysophosphatidic acid receptor 3) as a mediator for mitotic phosphorylation-driven pancreatic cell motility and invasion. Together, this work identifies YAP as a novel regulator of pancreatic cancer cell motility, invasion and metastasis, and as a potential therapeutic target for invasive pancreatic cancer.
DOI Link
ISSN
1949-2553
Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.
Recommended Citation
Yang, Shuping; Zhang, Lin; Purohit, Vinee; Shukla, Surendra K.; Chen, Xingcheng; Yu, Fang; Fu, Kai; Chen, Yuanhong; Solheim, Joyce C.; Shukla, Surendra K.; Song, Wei; and Dong, Jixin, "Active YAP promotes pancreatic cancer cell motility, invasion and tumorigenesis in a mitotic phosphorylation-dependent manner through LPAR3." (2015). Journal Articles: Eppley Institute. 6.
https://digitalcommons.unmc.edu/eppley_articles/6