Next Article in Journal
A Decade of Antifungal Leads from Natural Products: 2010–2019
Next Article in Special Issue
Mitogen-Activated Protein Kinase Inhibitors and T-Cell-Dependent Immunotherapy in Cancer
Previous Article in Journal
Metabolism and Pharmacokinetic Study of the Boron-Containing Prodrug of Belinostat (ZL277), a Pan HDAC Inhibitor with Enhanced Bioavailability
Previous Article in Special Issue
CDK8-Novel Therapeutic Opportunities
Open AccessArticle

Prostate-Derived ETS Factor (PDEF) Modulates Yes Associated Protein 1 (YAP1) in Prostate Cancer Cells: A Potential Cross-Talk between PDEF and Hippo Signaling

1
Department of Biochemistry and Molecular Biology, LSU Health Sciences Center Shreveport, LA 71130, USA
2
Department of Urology, LSU Health Sciences Center Shreveport, LA 71130, USA
3
Feist Weiller Cancer Center, LSU Health Sciences Center Shreveport, LA 71130, USA
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2019, 12(4), 181; https://doi.org/10.3390/ph12040181
Received: 19 October 2019 / Revised: 5 December 2019 / Accepted: 7 December 2019 / Published: 10 December 2019
(This article belongs to the Collection Protein Kinases and Cancer)
PDEF (prostate-derived ETS factor, also known as SAM-pointed domain containing ETS transcription factor (SPDEF)) is expressed in luminal epithelial cells of the prostate gland and associates with luminal phenotype. The Hippo pathway regulates cell growth/proliferation, cellular homeostasis, and organ development by modulating phosphorylation of its downstream effectors. In previous studies, we observed decreased levels of PDEF during prostate cancer progression. In the present study, we evaluated the effects of the expression of PDEF on total/phosphoprotein levels of YAP1 (a downstream effector of the Hippo pathway). We observed that the PC3 and DU145 cells transfected with PDEF (PDEF-PC3 and PDEF-DU145) showed an increased phospho-YAP1 (Ser127) and total YAP1 levels as compared to the respective PC3 vector control (VC-PC3) and DU145 vector control cells (VC-DU145). We also observed an increased cytoplasmic YAP1 levels in PDEF-PC3 cells as compared to VC-PC3 cells. Moreover, our gene set enrichment analysis (GSEA) of mRNA expression in PDEF-PC3 and VC-PC3 cells revealed that PDEF resulted in inhibition of YAP1 target genes, directly demonstrating that PDEF plays a critical role in modulating YAP1 activity, and by extension in the regulation of the Hippo pathway. We also observed a decrease in YAP1 mRNA levels in prostate cancer tissues as compared to normal prostate tissues. Our analysis of multiple publicly available clinical cohorts revealed a gradual decrease in YAP1 mRNA expression during prostate cancer progression and metastasis. This decrease was similar to the decrease in PDEF levels, which we had reported earlier, and we observed a direct correlation between PDEF and YAP1 expression in CRPC data set. To the best of our knowledge, these results provide the first demonstration of inhibiting YAP1 activity by PDEF in any system and suggest a cross-talk between PDEF and the Hippo signaling pathway. View Full-Text
Keywords: YAP1; PDEF; prostate cancer YAP1; PDEF; prostate cancer
Show Figures

Figure 1

MDPI and ACS Style

Jaiswal, P.K.; Mohajan, S.; Koul, S.; Wang, F.; Shi, R.; Koul, H.K. Prostate-Derived ETS Factor (PDEF) Modulates Yes Associated Protein 1 (YAP1) in Prostate Cancer Cells: A Potential Cross-Talk between PDEF and Hippo Signaling. Pharmaceuticals 2019, 12, 181.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop