ORIGINAL ARTICLE YAP1 Is Involved in Tumorigenic Properties of Prostate Cancer Cells Filiz Kisaayak Collak 1 & Ummuhan Demir 1 & Fatma Sagir 1 Received: 9 March 2018 /Accepted: 5 March 2019 # Arányi Lajos Foundation 2019 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. Keywords YAP1 . pYAP1 . Prostate cancer . Androgen receptor Introduction The Hippo pathway is a prominent tumor suppressor pathway controlling cell proliferation, cell death and differen- tiation [1, 2]. The Yes associated protein 1 (YAP1) is a tran- scription co-factor in the pathway regulating gene expression. Its function is mediated by the core components of the path- way kinases serine threonine kinase 1 and 2 (MST1/2) and the large tumor suppressor serine/threonine protein kinases 1 and 2 (LATS1/2) through phosphorylation. When the Hippo path- way is active, YAP1 is phosphorylated at serine 127 residue (S127). This phosphorylation causes inactivation of YAP1 by sequestration in the cytoplasm through binding to 14–3-3 binding proteins [3]. When the Hippo pathway is inactive, YAP1 translocates to the nucleus and drives the expression of genes together with transcription factors functioning as a transcription co-activator or co-repressor [4]. The best- characterized transcription factors regulated by YAP1 are the TEAD/TEF family transcription factors [ 5]. Besides TEAD, YAP1 also interacts with other transcription factors such as SMAD [6], p73 [7], ERBB4 [8]. Prostate cancer is the most common solid tumor remaining a leading common cause of death in males despite the early diag- nostic efforts [9]. The most common metastatic targets for pros- tate cancer cells are lymph nodes, bone, lung, and liver [10]. The reason for most of the deaths is the development of distant metastasis of prostate cancer cells to these sites. Androgen * Filiz Kisaayak Collak filiz.collak@medeniyet.edu.tr Ummuhan Demir ummuhan.demir@medeniyet.edu.tr Fatma Sagir fatma.sagir@medeniyet.edu.tr 1 Faculty of Engineering and Natural Sciences, Molecular Biology and Genetics Department, Istanbul Medeniyet University, 34700, Uskudar, Istanbul, Turkey Pathology & Oncology Research https://doi.org/10.1007/s12253-019-00634-z