Chen-Ying Liu‡,§, Tong Yu‡, Yuji Huang‡, Long Cui‡ and Wanjin Hong§
‡ Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
§ Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore
Published in J Biol Chem, Jun 2;292(22):9420-9430. Epub 2017 Apr 13.
Prostate cancer is a very common malignant disease and a leading cause of death for men in the Western world. Tumorigenesis and progression of prostate cancer involves multiple signaling pathways, including the Hippo pathway. Yes-associated protein (YAP) is the downstream transcriptional co-activator of the Hippo pathway, is overexpressed in prostate cancer, and plays a vital role in the tumorigenesis and progression of prostate cancer. However, the role of the YAP paralog and another downstream effector of the Hippo pathway, transcriptional co-activator with PDZ-binding motif (TAZ), in prostate cancer has not been fully elucidated. Here, we show that TAZ is a basal cell marker for the prostate epithelium. We found that overexpression of TAZ promotes the epithelial-mesenchymal transition (EMT), cell migration, and anchorage-independent growth in the RWPE1 prostate epithelial cells. Of note, knock down of TAZ in the DU145 prostate cancer cells inhibited cell migration and metastasis. We also found that SH3 domain binding protein 1 (SH3BP1), a RhoGAP protein that drives cell motility, is a direct target gene of TAZ in the prostate cancer cells, mediating TAZ function in enhancing cell migration. Moreover, the prostate cancer-related oncogenic E26 transformation-specific (ETS) transcription factors, ETV1, ETV4, and ETV5, were required for TAZ gene transcription in PC3 prostate cancer cells. MAPK inhibitor U0126 treatment decreased TAZ expression in RWPE1 cells, and ETV4 overexpression rescued TAZ expression in RWPE1 cells with U0126 treatment. Our results show a regulatory mechanism of TAZ transcription and suggest a significant role for TAZ in the progression of prostate cancer.
Figure legend: TAZ is a basal cell marker for prostate epithelium. (A) Immunohistochemical analysis of TAZ in normal prostate epithelium, hyperplasia and prostate cancer tissues. The representative images of TAZ in the normal prostate epithelium (a), TAZ in the hyperplasia tissue (b), no expression of TAZ in the prostate cancer tissue (c); strong expression of TAZ in some prostate cancer tissues (d) were shown. Scale bar: 50μm (a,c,d), 100μm (b). (B) The expression level of TAZ is positively associated with basal marker TP63 and negatively correlated with the luminal markers CK8 and CK18. Co-expression data in the prostate cancer TCGA dataset were extracted from the cbioportal database. The Pearson’s correlation coefficient and Spearman’s correlation coefficient values were generated by the cbioportal.
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