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TAZ promotes epithelial to mesenchymal transition via the upregulation of connective tissue growth factor expression in neuroblastoma cells.

Wang Q, Xu Z, An Q, Jiang D, Wang L, Liang B, Li Z - Mol Med Rep (2014)

Bottom Line: The Hippo signaling pathway regulates cell proliferation and apoptosis, and its primary downstream effectors are TAZ and yes‑associated protein 1 (YAP).Repressed expression of TAZ in SK‑N‑BE(2) cells was shown to result in a reduction in aggressiveness of the cell line, by Transwell migration and invasion assay.Furthermore, TAZ was shown by luciferase assay to induce CTGF expression by modulating the activation of the TGF‑β/Smad3 signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

ABSTRACT
Neuroblastoma (NB) is a neuroendocrine cancer that occurs most commonly in infants and young children. The Hippo signaling pathway regulates cell proliferation and apoptosis, and its primary downstream effectors are TAZ and yes‑associated protein 1 (YAP). The effect of TAZ on the metastatic progression of neuroblastoma and the underlying mechanisms involved remain elusive. In the current study, it was determined by western blot analysis that the migratory and invasive properties of SK‑N‑BE(2) human neuroblastoma cells are associated with high expression levels of TAZ. Repressed expression of TAZ in SK‑N‑BE(2) cells was shown to result in a reduction in aggressiveness of the cell line, by Transwell migration and invasion assay. In contrast, overexpression of TAZ in SK‑N‑SH human neuroblastoma cells was shown by Transwell migration and invasion assays, and western blot analysis, to result in epithelial‑mesenchymal transition (EMT) and increased invasiveness. Mechanistically, the overexpression of TAZ was demonstrated to upregulate the expression levels of connective tissue growth factor (CTGF), by western blot analysis and chromatin immunoprecipitation assay, while the knockdown of TAZ downregulated it. Furthermore, TAZ was shown by luciferase assay to induce CTGF expression by modulating the activation of the TGF‑β/Smad3 signaling pathway. In conclusion, the present study is, to the best of our knowledge, the first to demonstrate that the overexpression of TAZ induces EMT, increasing the invasive abilities of neuroblastoma cells. This suggests that TAZ may serve as a potential target in the development of novel therapies for the treatment of neuroblastoma.

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Repressed expression of TAZ in SK-N-BE(2) cells resulted in a reduced aggressiveness of the cell line. (A) The expression of TAZ was decreased through TAZ RNA interference (RNAi). (B) Expression levels of Vimentin, E-cadherin and β-catenin in TAZ-silenced SK-N-BE(2) cells. (C) Compared with the mock control, TAZ RNAi reduced the migratory ability of SK-N-BE(2) cells, as determined by Transwell® assays. (D) Compared with the mock control, TAZ RNAi reduced the invasion ability of SK-N-BE(2) cells, as determined by Transwell® assays.
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f2-mmr-11-02-0982: Repressed expression of TAZ in SK-N-BE(2) cells resulted in a reduced aggressiveness of the cell line. (A) The expression of TAZ was decreased through TAZ RNA interference (RNAi). (B) Expression levels of Vimentin, E-cadherin and β-catenin in TAZ-silenced SK-N-BE(2) cells. (C) Compared with the mock control, TAZ RNAi reduced the migratory ability of SK-N-BE(2) cells, as determined by Transwell® assays. (D) Compared with the mock control, TAZ RNAi reduced the invasion ability of SK-N-BE(2) cells, as determined by Transwell® assays.

Mentions: TAZ was knocked down by siRNA in the aggressive SK-N-BE(2) neuroblastoma cell line, which expresses high levels of TAZ. Knockdown of TAZ in SK-N-BE(2) cells resulted in a marked reduction at the TAZ protein expression level (Fig. 2A). Specific TAZ RNA interference (RNAi) suppressed the protein expression levels of the mesenchymal marker Vimentin. In contrast, the expression levels of the epithelial markers E-cadherin and β-catenin were increased (Fig. 2B). Compared with the mock control, the reduced expression of TAZ via RNAi reduced the migration and invasion abilities of SK-N-BE(2) cells (Fig. 2C and D).


TAZ promotes epithelial to mesenchymal transition via the upregulation of connective tissue growth factor expression in neuroblastoma cells.

Wang Q, Xu Z, An Q, Jiang D, Wang L, Liang B, Li Z - Mol Med Rep (2014)

Repressed expression of TAZ in SK-N-BE(2) cells resulted in a reduced aggressiveness of the cell line. (A) The expression of TAZ was decreased through TAZ RNA interference (RNAi). (B) Expression levels of Vimentin, E-cadherin and β-catenin in TAZ-silenced SK-N-BE(2) cells. (C) Compared with the mock control, TAZ RNAi reduced the migratory ability of SK-N-BE(2) cells, as determined by Transwell® assays. (D) Compared with the mock control, TAZ RNAi reduced the invasion ability of SK-N-BE(2) cells, as determined by Transwell® assays.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4262480&req=5

f2-mmr-11-02-0982: Repressed expression of TAZ in SK-N-BE(2) cells resulted in a reduced aggressiveness of the cell line. (A) The expression of TAZ was decreased through TAZ RNA interference (RNAi). (B) Expression levels of Vimentin, E-cadherin and β-catenin in TAZ-silenced SK-N-BE(2) cells. (C) Compared with the mock control, TAZ RNAi reduced the migratory ability of SK-N-BE(2) cells, as determined by Transwell® assays. (D) Compared with the mock control, TAZ RNAi reduced the invasion ability of SK-N-BE(2) cells, as determined by Transwell® assays.
Mentions: TAZ was knocked down by siRNA in the aggressive SK-N-BE(2) neuroblastoma cell line, which expresses high levels of TAZ. Knockdown of TAZ in SK-N-BE(2) cells resulted in a marked reduction at the TAZ protein expression level (Fig. 2A). Specific TAZ RNA interference (RNAi) suppressed the protein expression levels of the mesenchymal marker Vimentin. In contrast, the expression levels of the epithelial markers E-cadherin and β-catenin were increased (Fig. 2B). Compared with the mock control, the reduced expression of TAZ via RNAi reduced the migration and invasion abilities of SK-N-BE(2) cells (Fig. 2C and D).

Bottom Line: The Hippo signaling pathway regulates cell proliferation and apoptosis, and its primary downstream effectors are TAZ and yes‑associated protein 1 (YAP).Repressed expression of TAZ in SK‑N‑BE(2) cells was shown to result in a reduction in aggressiveness of the cell line, by Transwell migration and invasion assay.Furthermore, TAZ was shown by luciferase assay to induce CTGF expression by modulating the activation of the TGF‑β/Smad3 signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

ABSTRACT
Neuroblastoma (NB) is a neuroendocrine cancer that occurs most commonly in infants and young children. The Hippo signaling pathway regulates cell proliferation and apoptosis, and its primary downstream effectors are TAZ and yes‑associated protein 1 (YAP). The effect of TAZ on the metastatic progression of neuroblastoma and the underlying mechanisms involved remain elusive. In the current study, it was determined by western blot analysis that the migratory and invasive properties of SK‑N‑BE(2) human neuroblastoma cells are associated with high expression levels of TAZ. Repressed expression of TAZ in SK‑N‑BE(2) cells was shown to result in a reduction in aggressiveness of the cell line, by Transwell migration and invasion assay. In contrast, overexpression of TAZ in SK‑N‑SH human neuroblastoma cells was shown by Transwell migration and invasion assays, and western blot analysis, to result in epithelial‑mesenchymal transition (EMT) and increased invasiveness. Mechanistically, the overexpression of TAZ was demonstrated to upregulate the expression levels of connective tissue growth factor (CTGF), by western blot analysis and chromatin immunoprecipitation assay, while the knockdown of TAZ downregulated it. Furthermore, TAZ was shown by luciferase assay to induce CTGF expression by modulating the activation of the TGF‑β/Smad3 signaling pathway. In conclusion, the present study is, to the best of our knowledge, the first to demonstrate that the overexpression of TAZ induces EMT, increasing the invasive abilities of neuroblastoma cells. This suggests that TAZ may serve as a potential target in the development of novel therapies for the treatment of neuroblastoma.

Show MeSH
Related in: MedlinePlus