Increased expression of YAP1 in prostate cancer correlates with extraprostatic extension

Filiz Kisaayak Collak, Ummuhan Demir, Seyma Ozkanli, Esra Kurum, Pinar Engin Zerk


Objective: Yes associated protein 1 (YAP1) is a member of the Hippo pathway, acting as a transcriptional coactivator. To elucidatethe role of YAP1 and phosphorylated (p)YAP1 in prostate cancer (PCa) tumorigenesis, we investigated their expression in clinicalsamples of PCa and cell lines.

Methods: Fifty-four tumor, adjacent nontumor, and prostate intraepithelial neoplasia (PIN) tissues from patients with PCa afterradical prostatectomy were selected from a retrospective cohort and studied using immunohistochemistry (IHC). Protein andmRNA expression levels of YAP1 were evaluated by Western blot analysis and quantitative real-time reverse transcription PCR,respectively, in cancer cell lines. Publicly available gene expression datasets were downloaded to analyze YAP1 mRNA and proteinlevels in PCa tissue samples.

Results: IHC analysis of PCa tissues revealed that YAP1 staining intensities were moderate to weak in the nucleus and cytoplasm oftumor cells, whereas adjacent normal epithelia showed strong staining. We observed that benign prostates were characterized byhigher expression levels of both nuclear (P=0.004) and cytosolic (P=0.005) YAP1. pYAP1 staining was weak in the cytoplasm andabsent in the nucleus of all the tissues investigated. YAP1 expression was an indicator of extraprostatic extension (EPE). The levelof YAP1 was negatively correlated with the level of the androgen receptor (AR) in The Cancer Genome Atlas dataset and Westernblot analysis of cell lines.

Conclusions: Our study suggested that YAP1 expression is heterogeneous in PCa tissue samples; therefore, YAP1 might playdifferent roles in different aspects of PCa progression. This might involve AR–YAP1 interplay in PCa.


YAP1; pYAP1; PCa

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