YAP1 Is Involved in Tumorigenic Properties of Prostate Cancer Cells

Abstract

The Yes Associated Protein 1 (YAP1) is a transcriptional cofactor negatively regulated by Hippo Pathway. The dysregulation of the pathway has been shown to have a role in tumorigenesis and metastasis in several cancers including prostate cancer (PCa). In this study, YAP1 expression was upregulated in the whole cell lysates and cytoplasmic/nuclear extracts of AR negative (PC3) compared to AR positive (LNCaP) prostate cancer cell lines and primary prostate epithelial cells (PrePEC). pYAP1 expression elevated in LNCaP compared to PC3 and PrePEC in whole cell lysates and cytoplasmic extracts. The treatment of LNCaP and PC3 with YAP1-targeting siRNA oligonucleotides (YAP1 siRNA) significantly reduced their proliferation in vitro. Furthermore, treatment with YAP1 siRNA diminished the clonogenicity, anchorage-independent growth on soft agar, migration and invasion of PC3 cells. Co-IP/WB experiments revealed that YAP1 and AR formed a complex and ChIP/PCR results confirmed that YAP1 was bound to androgen response elements (ARE) core region of the prostate specific antigen (PSA) promoter. The loss of function experiments in LNCaP and PC3 revealed that YAP1 regulates proliferation, colony formation as well as anchorage-independent growth and potentially plays an important role in migration and invasion. Finally, analysis of publicly available data sets indicated that LNCaP had no YAP1 copy number alteration whereas PC3 had gain of YAP1 which was also reflected as an increase in the mRNA level. Moreover, YAP1 copy number gain and elevated YAP1 mRNA expression were detected in clinical samples analyzed in publicly available data sets. Taken together, these results suggested that YAP1 has a role in PCa tumorigenesis.