PRDM 4 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 () 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 expression and cell invasion. Consistently, and 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.

Intracellular Fate and Impact on Gene Expression of Doxorubicin/Cyclodextrin-Graphene Nanomaterials at Sub-Toxic Concentration

“…ITGB2 expression in cancer cells promotes cell invasion through the endothelium in leukocyte-like manner. ITGB2 levels are significantly increased in metastatic prostate cancer [50]. Notably, the observed GCD-induced down-regulation of ITGB2 confirms previously reported effects of graphene on integrin suppression linked to plasma membrane and cytoskeleton meshwork perturbation [51].…”

Analysis of Copy-Number Variations and Feline Mammary Carcinoma Survival

“…Genes in this region enriched the leukocyte transendothelial migration pathway. The similarities in the molecular mechanisms behind the first steps of leukocytes and neoplastic cells extravasation are well known 85,86 . Moreover, this region encompasses up to 50 genes implicated in actin cytoskeleton organization and cellular motion including SBDS, ITGAM, PDGFA, and RAC1 49 .…”

Periostin Promotes Colorectal Tumorigenesis through Integrin-FAK-Src Pathway-Mediated YAP/TAZ Activation

“…When reaching 60% confluence, cells were subjected to 100 nM final concentration of siRNAs. siRNAs were purchased from Sangon Biotech (Shanghai, China), and the sequences of the siRNAs were listed in Key Resources Table. pCMV5-Flag-YAP wild-type and pCMV5-Flag-YAP 5SA plasmids were used as described previously (Liu et al, 2018).…”