@article{d7a4a4a9a3b24b43b862085030f070e3,
title = "PRDM4 mediates YAP-induced cell invasion by activating leukocyte-specific integrin β2 expression",
abstract = "Yes-associated protein (YAP) is a transcriptional co-activator and a major effector of the Hippo pathway that promotes cell proliferation and stemness, while inhibiting apoptosis. YAP plays a central role in organ size control, and its deregulation strongly promotes cancer initiation and progression. However, the mechanisms by which YAP promotes cell invasion and metastasis are not fully understood. Here, we report that YAP induces leukocyte-specific integrin β2 (ITGB2) expression in cancer cells, thereby promoting cell invasion through the endothelium in a manner mimicking leukocytes. Through independent biochemical purification and a functional screen, we further identified PR/SET domain 4 (PRDM4) as a transcription factor interacting with the WW domains of YAP to mediate ITGB2 expression and cell invasion. Consistently, ITGB2 and PRDM4 mRNA levels are significantly increased in metastatic prostate cancer. In addition, PRDM4 contributes to YAP-induced tumorigenesis possibly via mediating the expression of other YAP target genes. Our results demonstrate that YAP promotes cell invasion by inducing leukocyte-specific integrin expression, and identify PRDM4 as a novel transcription factor for YAP targets.",
keywords = "Hippo pathway, ITGB2, PRDM4, cell invasion, yes-associated protein",
author = "Huan Liu and Xiaoming Dai and Xiaolei Cao and Huan Yan and Xinyan Ji and Haitao Zhang and Shuying Shen and Yuan Si and Hailong Zhang and Jianfeng Chen and Li Li and Zhao, {Jonathan C.} and Jindan Yu and Feng, {Xin Hua} and Bin Zhao",
note = "Funding Information: We thank Dr. Kun-Liang Guan for critical reagents; Dr. Hongbin Ji for HTB182 and CRL1848 cell lines; Dr. Hengyu Fan for ES-2 cell line; and Dr. Zongping Xia for PEP-KO and pGL4.21-TATA vectors. The results are in part based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/. The dbGaP project provided access to the datasets (accession nos.: phs000443, phs000915, and phs000909). This work was supported by grants to B. Zhao from the National Key R&D Program of China (2017YFA0504502), the National Natural Science Foundation of China General Project (31471316), Key Project (81730069), and International Collaboration Project (31661130150), the 111 project (B13026), the Fundamental Research Funds for the Central Universities, the Qianjiang Scholar?Plan of Hangzhou, the Thousand Young Talents Plan of China, and the Newton Advanced Fellowship from the Academy of Medical Sciences, UK. Funding Information: We thank Dr. Kun-Liang Guan for critical reagents; Dr. Hongbin Ji for HTB182 and CRL1848 cell lines; Dr. Hengyu Fan for ES-2 cell line; and Dr. Zongping Xia for PEP-KO and pGL4.21-TATA vectors. The results are in part based upon data generated by the TCGA Research Network: http://cancerge nome.nih.gov/. The dbGaP project provided access to the datasets (accession nos.: phs000443, phs000915, and phs000909). This work was supported by grants to B. Zhao from the National Key R&D Program of China (2017YFA0504502), the National Natural Science Foundation of China General Project (31471316), Key Project (81730069), and International Collaboration Project (31661130150), the 111 project (B13026), the Fundamental Research Funds for the Central Universities, the Qianjiang Scholar Plan of Hangzhou, the Thousand Young Talents Plan of China, and the Newton Advanced Fellowship from the Academy of Medical Sciences, UK. Publisher Copyright: {\textcopyright} 2018 The Authors",
year = "2018",
month = jun,
doi = "10.15252/embr.201745180",
language = "English (US)",
volume = "19",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "6",
}
