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PRDM 4 mediates YAP ‐induced cell invasion by activating leukocyte‐specific integrin β2 expression
Author(s) -
Liu Huan,
Dai Xiaoming,
Cao Xiaolei,
Yan Huan,
Ji Xinyan,
Zhang Haitao,
Shen Shuying,
Si Yuan,
Zhang Hailong,
Chen Jianfeng,
Li Li,
Zhao Jonathan C,
Yu Jindan,
Feng XinHua,
Zhao Bin
Publication year - 2018
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201745180
Subject(s) - china , chinese academy of sciences , library science , biology , political science , computer science , law
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 ( ITGB 2 ) 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 ( PRDM 4) as a transcription factor interacting with the WW domains of YAP to mediate ITGB 2 expression and cell invasion. Consistently, ITGB 2 and PRDM 4 mRNA levels are significantly increased in metastatic prostate cancer. In addition, PRDM 4 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 PRDM 4 as a novel transcription factor for YAP targets.