ETS (E26 transformation-specific) up-regulation of the transcriptional co-activator TAZ promotes cell migration and metastasis in prostate cancer

J Biol Chem. 2017 Jun 2;292(22):9420-9430. doi: 10.1074/jbc.M117.783787. Epub 2017 Apr 13.

Abstract

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.

Keywords: ETS transcription factor family; Hippo pathway; SH3BP1; TAZ; cell migration; prostate cancer; tumor metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adenovirus E1A Proteins / genetics
  • Adenovirus E1A Proteins / metabolism*
  • Animals
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Adenovirus E1A Proteins
  • DNA-Binding Proteins
  • ETV1 protein, human
  • ETV4 protein, human
  • ETV5 protein, human
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • TAZ protein, human
  • Transcription Factors
  • YAP1 (Yes-associated) protein, human