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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

TAZ-knockdown inhibits cell proliferation and migration, and induces epithelial-mesenchymal transition in ovarian cancer cells. SKOV-3 cells were transfected with siRNA targeting human TAZ and control siRNA. (A) At 48 h post-transfection, the cells were plated into 96-well plates and the cell numbers were detected by Cell Counting kit-8 assay. (B) Migratory ability of the SKOV-3 cells, as detected by Transwell assay. Representative images (×100 magnification) of each group are shown. Crystal violet staining. *P<0.05 vs. con, Student's t-test. (C) Western blot analysis of SKOV-3 cells transfected with indicated siRNA 72 h post-transfection. OD, optical density; siRNA, small interfering RNA; CON, control; TAZ, tafazzin; ZO, zonula occludens; VIM, vimentin; YAP, yes-associated protein 1.
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f2-ol-0-0-4829: TAZ-knockdown inhibits cell proliferation and migration, and induces epithelial-mesenchymal transition in ovarian cancer cells. SKOV-3 cells were transfected with siRNA targeting human TAZ and control siRNA. (A) At 48 h post-transfection, the cells were plated into 96-well plates and the cell numbers were detected by Cell Counting kit-8 assay. (B) Migratory ability of the SKOV-3 cells, as detected by Transwell assay. Representative images (×100 magnification) of each group are shown. Crystal violet staining. *P<0.05 vs. con, Student's t-test. (C) Western blot analysis of SKOV-3 cells transfected with indicated siRNA 72 h post-transfection. OD, optical density; siRNA, small interfering RNA; CON, control; TAZ, tafazzin; ZO, zonula occludens; VIM, vimentin; YAP, yes-associated protein 1.

Mentions: To investigate the function of TAZ in ovarian cancer cells, two siRNAs targeting human TAZ were transfected into SKOV-3 cells and cell proliferation was analyzed following transfection. Transfecting each TAZ siRNA either individually or in combination resulted in a significant decrease in the proliferation of the SKOV-3 cells (P=0.00004, siRNA-TAZ-1+2 vs. siRNA-CON; Fig. 2A). Next, the current study performed Transwell assays to determine whether TAZ-knockdown affects the migratory ability of ovarian cancer cells. As presented in Fig. 2B, knockdown of TAZ in the SKOV-3 cells largely decreased their migratory ability compared with control cells (P=0.000089). Overexpression of TAZ in breast cancer promotes EMT (13,14), therefore, the protein expression levels of several EMT markers were also examined in the TAZ-knockdown cancer cells. Although no changes were observed in canonical EMT markers, including E-cadherin and N-cadherin (data not shown), a moderate increase in the expression level of epithelial marker ZO-1 and a decrease in the level of mesenchymal marker vimentin were identified in TAZ-knockdown versus control cells (Fig. 2C). These results indicate that mesenchymal-epithelial transition was induced by TAZ-knockdown in the SKOV-3 cells. Taken together, the data suggests that TAZ serves a vital role in promoting proliferation, migration and EMT in ovarian cancer cells.


Overexpression of TAZ promotes cell proliferation, migration and epithelial-mesenchymal transition in ovarian cancer
TAZ-knockdown inhibits cell proliferation and migration, and induces epithelial-mesenchymal transition in ovarian cancer cells. SKOV-3 cells were transfected with siRNA targeting human TAZ and control siRNA. (A) At 48 h post-transfection, the cells were plated into 96-well plates and the cell numbers were detected by Cell Counting kit-8 assay. (B) Migratory ability of the SKOV-3 cells, as detected by Transwell assay. Representative images (×100 magnification) of each group are shown. Crystal violet staining. *P<0.05 vs. con, Student's t-test. (C) Western blot analysis of SKOV-3 cells transfected with indicated siRNA 72 h post-transfection. OD, optical density; siRNA, small interfering RNA; CON, control; TAZ, tafazzin; ZO, zonula occludens; VIM, vimentin; YAP, yes-associated protein 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

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f2-ol-0-0-4829: TAZ-knockdown inhibits cell proliferation and migration, and induces epithelial-mesenchymal transition in ovarian cancer cells. SKOV-3 cells were transfected with siRNA targeting human TAZ and control siRNA. (A) At 48 h post-transfection, the cells were plated into 96-well plates and the cell numbers were detected by Cell Counting kit-8 assay. (B) Migratory ability of the SKOV-3 cells, as detected by Transwell assay. Representative images (×100 magnification) of each group are shown. Crystal violet staining. *P<0.05 vs. con, Student's t-test. (C) Western blot analysis of SKOV-3 cells transfected with indicated siRNA 72 h post-transfection. OD, optical density; siRNA, small interfering RNA; CON, control; TAZ, tafazzin; ZO, zonula occludens; VIM, vimentin; YAP, yes-associated protein 1.
Mentions: To investigate the function of TAZ in ovarian cancer cells, two siRNAs targeting human TAZ were transfected into SKOV-3 cells and cell proliferation was analyzed following transfection. Transfecting each TAZ siRNA either individually or in combination resulted in a significant decrease in the proliferation of the SKOV-3 cells (P=0.00004, siRNA-TAZ-1+2 vs. siRNA-CON; Fig. 2A). Next, the current study performed Transwell assays to determine whether TAZ-knockdown affects the migratory ability of ovarian cancer cells. As presented in Fig. 2B, knockdown of TAZ in the SKOV-3 cells largely decreased their migratory ability compared with control cells (P=0.000089). Overexpression of TAZ in breast cancer promotes EMT (13,14), therefore, the protein expression levels of several EMT markers were also examined in the TAZ-knockdown cancer cells. Although no changes were observed in canonical EMT markers, including E-cadherin and N-cadherin (data not shown), a moderate increase in the expression level of epithelial marker ZO-1 and a decrease in the level of mesenchymal marker vimentin were identified in TAZ-knockdown versus control cells (Fig. 2C). These results indicate that mesenchymal-epithelial transition was induced by TAZ-knockdown in the SKOV-3 cells. Taken together, the data suggests that TAZ serves a vital role in promoting proliferation, migration and EMT in 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