The laboratory headed by ZHAO Bin with the Life Sciences Institute and Innovation Center for Cell Signaling Network published a cover article entitled “PRDM4 mediates YAP-induced cell invasion by activating leukocyte-specific integrinb2 expression” in EMBO Reports in June 2018.
The Hippo pathway plays an evolutionarily conserved role in organ size control. Mutations in this pathway lead to characteristic enlargement of organ size due to enhanced cell proliferation, reduced apoptosis, and expansion of tissue-specific progenitor cells. 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.
ZHAO Bin et al. report that YAP induces leukocyte-specific integrin β2 (ITGB2) expression in cancer cells, thereby promoting cell invasion through the endothelium by mimicking leukocytes. Through independent biochemical purification and a functional screen, they further identify 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.
Their findings demonstrate that YAP promotes cell invasion by inducing leukocyte-specific integrin expression, and PRDM4 is identified as a novel transcription factor for YAP targets.