ETS dependent transcriptional upregulation of the transcriptional co-activator TAZ promotes cell migration and metastasis in prostate cancer [Molecular Bases of Disease]

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 Hippo pathway. Yes-associated protein (YAP) is the downstream transcriptional co-activator of Hippo pathway, is overexpressed in the prostate cancer, and plays a vital role in the tumorigenesis and cancer progression of prostate cancer. However, the role of the YAP paralog and another downstream effector of 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 promoted the epithelial-mesenchymal transition (EMT), cell migration, and anchorage-independent growth in the RWPE1 prostate epithelial cells. Of note, knockdown 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's function in enhancing cell migration. Moreover, the prostate cancer related oncogenic E26 transformation-specific (ETS) transcription factors, ETV1/4/5, 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 of TAZ in the progression of prostate cancer.

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