The expression of YAP1 is increased in high-grade prostatic adenocarcinoma but is reduced in neuroendocrine prostate cancer

Abstract

Background

After long-term androgen deprivation therapy, 25–30% prostate cancer (PCa) acquires an aggressive neuroendocrine (NE) phenotype. Dysregulation of YAP1, a key transcription coactivator of the Hippo pathway, has been related to cancer progression. However, its role in neuroendocrine prostate cancer (NEPC) has not been assessed.

Methods

Immunohistochemistry and bioinformatics analysis were conducted to evaluate YAP1 expression levels during PCa initiation and progression.

Results

YAP1 expression was present in the basal epithelial cells in benign prostatic tissues, lost in low-grade PCa, but elevated in high-grade prostate adenocarcinomas. Interestingly, the expression of YAP1 was reduced/lost in both human and mouse NEPC.

Conclusions

The expression of YAP1 is elevated in high-grade prostate adenocarcinomas but lost in NEPC.

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Fig. 1: The expression of YAP1 in benign prostatic hyperplasia.
Fig. 2: Microscopic examination of the prostate of TRAMP and LADY mice revealed that the expression of YAP1 increased in PIN but decreased in NEPC.
Fig. 3: The expression of YAP1 in human prostatic tissues.
Fig. 4: The differential expression of YAP1 in PCa.

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Acknowledgements

We thank Dr Robert Matusik at Vanderbilt University for providing tissues of LADY mice and advice on this research. This research was supported by NIH R03 CA212567, R01 CA226285, U54 GM104940, DOD W81XWH-12-1-0212, and LSUHSC FWCC and Office of Research funding to XY.

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Correspondence to Xiuping Yu.

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Cheng, S., Prieto-Dominguez, N., Yang, S. et al. The expression of YAP1 is increased in high-grade prostatic adenocarcinoma but is reduced in neuroendocrine prostate cancer. Prostate Cancer Prostatic Dis (2020). https://doi.org/10.1038/s41391-020-0229-z

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