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Overexpression of TAZ promotes cell proliferation, migration and epithelial-mesenchymal transition in ovarian cancer

View Article: PubMed Central - PubMed

ABSTRACT

The Hippo pathway is dysregulated in multiple types of human cancer, including ovarian cancer. Nuclear expression of yes-associated protein 1 (YAP1), a downstream transcription coactivator of the Hippo pathway, has been demonstrated to promote tumorigenesis in ovarian cancer and may serve as a poor prognostic indicator. However, transcriptional coactivator with PDZ binding motif (TAZ), a downstream target of the Hippo pathway and paralog of YAP in mammalian cells, has not been fully investigated in ovarian cancer. The present study aimed to investigate the dysregulation and biological function of TAZ in ovarian cancer. Reverse transcription-quantitative polymerase chain reaction and western blotting revealed that TAZ mRNA and protein levels, respectively, were upregulated in ovarian cancer, and a meta-analysis of ovarian cancer microarray datasets identified that increased expression of TAZ mRNA is correlated with poor prognosis in patients with ovarian cancer. In addition, TAZ-knockdown in ovarian cancer cells demonstrated that TAZ regulates the migration, proliferation and epithelial-mesenchymal transition of ovarian cancer cells. Furthermore, pharmacological disruption of the YAP/TAZ/TEA domain protein complex resulted in a decrease in ovarian cancer cell migration, proliferation and vimentin expression. The results of the present study indicate that the overexpression of TAZ is important in the development and progression of ovarian cancer, and may function as a potential drug target for treatment of this disease entity.

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Related in: MedlinePlus

TAZ is overexpressed in and correlated with a poor prognosis in patients with ovarian cancer. (A) Reverse transcription-quantitative polymerase chain reaction analysis of TAZ mRNA expression levels and (B) western blot analysis of TAZ protein expression levels in the 7 ovarian cancer samples and paired normal tissues. Kaplan-Meier plots of the (C) progression-free and (D) overall survival time of patients with ovarian cancer stratified by TAZ mRNA expression level, constructed using KMplot (http://kmplot.com/analysis). The log-rank test was performed to assess statistical significance of survival data. N, normal; C, cancer; TAZ, tafazzin; HR, hazard ratio.
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f1-ol-0-0-4829: TAZ is overexpressed in and correlated with a poor prognosis in patients with ovarian cancer. (A) Reverse transcription-quantitative polymerase chain reaction analysis of TAZ mRNA expression levels and (B) western blot analysis of TAZ protein expression levels in the 7 ovarian cancer samples and paired normal tissues. Kaplan-Meier plots of the (C) progression-free and (D) overall survival time of patients with ovarian cancer stratified by TAZ mRNA expression level, constructed using KMplot (http://kmplot.com/analysis). The log-rank test was performed to assess statistical significance of survival data. N, normal; C, cancer; TAZ, tafazzin; HR, hazard ratio.

Mentions: TAZ is a paralog of YAP in mammalian cells (3,4) and dysregulation of YAP has been reported in ovarian cancer; however, the function of TAZ in ovarian cancer has not yet been investigated. To understand the dysregulation of TAZ in ovarian cancer, the expression of TAZ mRNA was analyzed in 7 ovarian cancer and paired normal tissue samples. Notably, as presented in Fig. 1A, TAZ mRNA was upregulated in 6/7 ovarian cancer samples compared with the paired normal tissues. Western blot analysis of these 7 paired cancer and normal tissues also showed that TAZ protein was overexpressed in 5/7 ovarian cancer tissues (Fig. 1B). These results suggest that TAZ mRNA and protein expression are upregulated in ovarian cancer. To investigate the association between upregulated TAZ expression and the prognosis of patients with ovarian cancer, the present study analyzed a public online database (12) integrating 13 public datasets with 1,305 cases with progression-free data and 1,581 cases with overall survival data, and observed that high expression of TAZ mRNA was a significant indicator of poor prognosis in ovarian cancer. Patients with a high expression level of TAZ mRNA had a shorter period of progression-free (P=0.000035; Fig. 1C) and overall survival (P=0.0048; Fig. 1D).


Overexpression of TAZ promotes cell proliferation, migration and epithelial-mesenchymal transition in ovarian cancer
TAZ is overexpressed in and correlated with a poor prognosis in patients with ovarian cancer. (A) Reverse transcription-quantitative polymerase chain reaction analysis of TAZ mRNA expression levels and (B) western blot analysis of TAZ protein expression levels in the 7 ovarian cancer samples and paired normal tissues. Kaplan-Meier plots of the (C) progression-free and (D) overall survival time of patients with ovarian cancer stratified by TAZ mRNA expression level, constructed using KMplot (http://kmplot.com/analysis). The log-rank test was performed to assess statistical significance of survival data. N, normal; C, cancer; TAZ, tafazzin; HR, hazard ratio.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4997911&req=5

f1-ol-0-0-4829: TAZ is overexpressed in and correlated with a poor prognosis in patients with ovarian cancer. (A) Reverse transcription-quantitative polymerase chain reaction analysis of TAZ mRNA expression levels and (B) western blot analysis of TAZ protein expression levels in the 7 ovarian cancer samples and paired normal tissues. Kaplan-Meier plots of the (C) progression-free and (D) overall survival time of patients with ovarian cancer stratified by TAZ mRNA expression level, constructed using KMplot (http://kmplot.com/analysis). The log-rank test was performed to assess statistical significance of survival data. N, normal; C, cancer; TAZ, tafazzin; HR, hazard ratio.
Mentions: TAZ is a paralog of YAP in mammalian cells (3,4) and dysregulation of YAP has been reported in ovarian cancer; however, the function of TAZ in ovarian cancer has not yet been investigated. To understand the dysregulation of TAZ in ovarian cancer, the expression of TAZ mRNA was analyzed in 7 ovarian cancer and paired normal tissue samples. Notably, as presented in Fig. 1A, TAZ mRNA was upregulated in 6/7 ovarian cancer samples compared with the paired normal tissues. Western blot analysis of these 7 paired cancer and normal tissues also showed that TAZ protein was overexpressed in 5/7 ovarian cancer tissues (Fig. 1B). These results suggest that TAZ mRNA and protein expression are upregulated in ovarian cancer. To investigate the association between upregulated TAZ expression and the prognosis of patients with ovarian cancer, the present study analyzed a public online database (12) integrating 13 public datasets with 1,305 cases with progression-free data and 1,581 cases with overall survival data, and observed that high expression of TAZ mRNA was a significant indicator of poor prognosis in ovarian cancer. Patients with a high expression level of TAZ mRNA had a shorter period of progression-free (P=0.000035; Fig. 1C) and overall survival (P=0.0048; Fig. 1D).

View Article: PubMed Central - PubMed

ABSTRACT

The Hippo pathway is dysregulated in multiple types of human cancer, including ovarian cancer. Nuclear expression of yes-associated protein 1 (YAP1), a downstream transcription coactivator of the Hippo pathway, has been demonstrated to promote tumorigenesis in ovarian cancer and may serve as a poor prognostic indicator. However, transcriptional coactivator with PDZ binding motif (TAZ), a downstream target of the Hippo pathway and paralog of YAP in mammalian cells, has not been fully investigated in ovarian cancer. The present study aimed to investigate the dysregulation and biological function of TAZ in ovarian cancer. Reverse transcription-quantitative polymerase chain reaction and western blotting revealed that TAZ mRNA and protein levels, respectively, were upregulated in ovarian cancer, and a meta-analysis of ovarian cancer microarray datasets identified that increased expression of TAZ mRNA is correlated with poor prognosis in patients with ovarian cancer. In addition, TAZ-knockdown in ovarian cancer cells demonstrated that TAZ regulates the migration, proliferation and epithelial-mesenchymal transition of ovarian cancer cells. Furthermore, pharmacological disruption of the YAP/TAZ/TEA domain protein complex resulted in a decrease in ovarian cancer cell migration, proliferation and vimentin expression. The results of the present study indicate that the overexpression of TAZ is important in the development and progression of ovarian cancer, and may function as a potential drug target for treatment of this disease entity.

No MeSH data available.


Related in: MedlinePlus