PRDM4 mediates YAP-induced cell invasion by activating leukocyte-specific integrin β2 expression

Huan Liu, Xiaoming Dai, Xiaolei Cao, Huan Yan, Xinyan Ji, Haitao Zhang, Shuying Shen, Yuan Si, Hailong Zhang, Jianfeng Chen, Li Li, Jonathan C. Zhao, Jindan Yu, Xin Hua Feng, Bin Zhao*

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Article numbere45180
JournalEMBO Reports
Volume19
Issue number6
DOIs
StatePublished - Jun 2018

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Keywords

  • Hippo pathway
  • ITGB2
  • PRDM4
  • cell invasion
  • yes-associated protein

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Liu, H., Dai, X., Cao, X., Yan, H., Ji, X., Zhang, H., Shen, S., Si, Y., Zhang, H., Chen, J., Li, L., Zhao, J. C., Yu, J., Feng, X. H., & Zhao, B. (2018). PRDM4 mediates YAP-induced cell invasion by activating leukocyte-specific integrin β2 expression. EMBO Reports, 19(6), [e45180]. https://doi.org/10.15252/embr.201745180