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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.

No MeSH data available.


Related in: MedlinePlus

Pharmacological inhibition of taffazin/TEA domain interactions decreases cell viability and migration, and induces EMT in ovarian cancer cells. SKOV-3 cells were treated with the indicated concentrations of verteporfin for 24 h prior to analysis. (A) Cell viability was analyzed by Cell Counting kit-8 assay. (B) Cell migration was analyzed by Transwell assay. Representative images (×100 magnification) of each group are shown. Crystal violet staining. *P<0.05, Student's t-test. (C) Protein expression was analyzed by western blotting. DMSO, dimethyl sulfoxide; VIM, vimentin; ZO-1, zonula occludens-1.
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f3-ol-0-0-4829: Pharmacological inhibition of taffazin/TEA domain interactions decreases cell viability and migration, and induces EMT in ovarian cancer cells. SKOV-3 cells were treated with the indicated concentrations of verteporfin for 24 h prior to analysis. (A) Cell viability was analyzed by Cell Counting kit-8 assay. (B) Cell migration was analyzed by Transwell assay. Representative images (×100 magnification) of each group are shown. Crystal violet staining. *P<0.05, Student's t-test. (C) Protein expression was analyzed by western blotting. DMSO, dimethyl sulfoxide; VIM, vimentin; ZO-1, zonula occludens-1.

Mentions: YAP/TAZ have been demonstrated to promote the tumorigenesis and progression of multiple types of cancer primarily through TEAD family members (14,15), therefore, disrupting the interaction between YAP/TAZ and TEAD may serve as a promising target for new drugs. Verteporfin, a drug used previously for the treatment of macular degeneration, was identified to disrupt the YAP/TEAD complex (16,17). The present study observed that verteporfin treatment results in decreased SKOV-3 cell viability (P=0.0014, 3 vs. 0 µM) Fig. 3A). Furthermore, verteporfin treatment significantly decreased and nearly abolished the migratory ability of the SKOV-3 cells (P=0.0000043; Fig. 3B). Similar to the effect of TAZ-knockdown on the SKOV-3 cells, the current study observed markedly decreased vimentin expression levels in the SKOV-3 cells following verteporfin treatment (Fig. 3C). These results indicate that disruption of the YAP/TAZ/TEAD complex mimics the effect of TAZ-knockdown in SKOV-3 ovarian cancer cells.


Overexpression of TAZ promotes cell proliferation, migration and epithelial-mesenchymal transition in ovarian cancer
Pharmacological inhibition of taffazin/TEA domain interactions decreases cell viability and migration, and induces EMT in ovarian cancer cells. SKOV-3 cells were treated with the indicated concentrations of verteporfin for 24 h prior to analysis. (A) Cell viability was analyzed by Cell Counting kit-8 assay. (B) Cell migration was analyzed by Transwell assay. Representative images (×100 magnification) of each group are shown. Crystal violet staining. *P<0.05, Student's t-test. (C) Protein expression was analyzed by western blotting. DMSO, dimethyl sulfoxide; VIM, vimentin; ZO-1, zonula occludens-1.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-ol-0-0-4829: Pharmacological inhibition of taffazin/TEA domain interactions decreases cell viability and migration, and induces EMT in ovarian cancer cells. SKOV-3 cells were treated with the indicated concentrations of verteporfin for 24 h prior to analysis. (A) Cell viability was analyzed by Cell Counting kit-8 assay. (B) Cell migration was analyzed by Transwell assay. Representative images (×100 magnification) of each group are shown. Crystal violet staining. *P<0.05, Student's t-test. (C) Protein expression was analyzed by western blotting. DMSO, dimethyl sulfoxide; VIM, vimentin; ZO-1, zonula occludens-1.
Mentions: YAP/TAZ have been demonstrated to promote the tumorigenesis and progression of multiple types of cancer primarily through TEAD family members (14,15), therefore, disrupting the interaction between YAP/TAZ and TEAD may serve as a promising target for new drugs. Verteporfin, a drug used previously for the treatment of macular degeneration, was identified to disrupt the YAP/TEAD complex (16,17). The present study observed that verteporfin treatment results in decreased SKOV-3 cell viability (P=0.0014, 3 vs. 0 µM) Fig. 3A). Furthermore, verteporfin treatment significantly decreased and nearly abolished the migratory ability of the SKOV-3 cells (P=0.0000043; Fig. 3B). Similar to the effect of TAZ-knockdown on the SKOV-3 cells, the current study observed markedly decreased vimentin expression levels in the SKOV-3 cells following verteporfin treatment (Fig. 3C). These results indicate that disruption of the YAP/TAZ/TEAD complex mimics the effect of TAZ-knockdown in SKOV-3 ovarian cancer cells.

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