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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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Related in: MedlinePlus

Overexpression of TAZ in SK-N-SH cells results in epithelial-to-mesenchymal transition and increased invasiveness. (A) The expression of TAZ was increased by overexpression of human influenza hemagglutinin-tagged TAZ in SK-N-SH cells. (B) Expression levels of Vimentin, E-cadherin and β-catenin in TAZ-expressing SK-N-SH cells. Compared with the mock control, TAZ overexpression increased the (C) migration and (D) invasion ability of SK-N-SH cells, which was determined by Transwell® assays.
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f3-mmr-11-02-0982: Overexpression of TAZ in SK-N-SH cells results in epithelial-to-mesenchymal transition and increased invasiveness. (A) The expression of TAZ was increased by overexpression of human influenza hemagglutinin-tagged TAZ in SK-N-SH cells. (B) Expression levels of Vimentin, E-cadherin and β-catenin in TAZ-expressing SK-N-SH cells. Compared with the mock control, TAZ overexpression increased the (C) migration and (D) invasion ability of SK-N-SH cells, which was determined by Transwell® assays.

Mentions: SK-N-SH cells overexpressing TAZ expressed increased levels of the mesenchymal marker Vimentin, and reduced levels of epithelial markers, including E-cadherin and β-catenin, compared with those in the mock control (Fig 3A and B). To determine if the TAZ-induced EMT-like phenotype could be translated into the aggressive ability of the SK-N-SH cells, the migration and invasion of SK-N-SH cells was investigated. SK-N-SH cells overexpressing TAZ showed an increase in motility in the migration and invasion assays, compared with that of the mock control cells (Fig. 3C 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)

Overexpression of TAZ in SK-N-SH cells results in epithelial-to-mesenchymal transition and increased invasiveness. (A) The expression of TAZ was increased by overexpression of human influenza hemagglutinin-tagged TAZ in SK-N-SH cells. (B) Expression levels of Vimentin, E-cadherin and β-catenin in TAZ-expressing SK-N-SH cells. Compared with the mock control, TAZ overexpression increased the (C) migration and (D) invasion ability of SK-N-SH cells, which was determined by Transwell® assays.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-mmr-11-02-0982: Overexpression of TAZ in SK-N-SH cells results in epithelial-to-mesenchymal transition and increased invasiveness. (A) The expression of TAZ was increased by overexpression of human influenza hemagglutinin-tagged TAZ in SK-N-SH cells. (B) Expression levels of Vimentin, E-cadherin and β-catenin in TAZ-expressing SK-N-SH cells. Compared with the mock control, TAZ overexpression increased the (C) migration and (D) invasion ability of SK-N-SH cells, which was determined by Transwell® assays.
Mentions: SK-N-SH cells overexpressing TAZ expressed increased levels of the mesenchymal marker Vimentin, and reduced levels of epithelial markers, including E-cadherin and β-catenin, compared with those in the mock control (Fig 3A and B). To determine if the TAZ-induced EMT-like phenotype could be translated into the aggressive ability of the SK-N-SH cells, the migration and invasion of SK-N-SH cells was investigated. SK-N-SH cells overexpressing TAZ showed an increase in motility in the migration and invasion assays, compared with that of the mock control cells (Fig. 3C 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