Journal
EMBO REPORTS
Volume 19, Issue 6, Pages -Publisher
WILEY
DOI: 10.15252/embr.201745180
Keywords
cell invasion; Hippo pathway; ITGB2; PRDM4; yes-associated protein
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Funding
- National Key RAMP
- D Program of China [2017YFA0504502]
- National Natural Science Foundation of China [31471316, 81730069]
- International Collaboration Project [31661130150]
- 111 project [B13026]
- Fundamental Research Funds for the Central Universities
- Qianjiang Scholar Plan of Hangzhou
- Thousand Young Talents Plan of China
- Academy of Medical Sciences, UK
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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 2 (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.
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