The role of transcriptional coactivator TAZ in gliomas

Abstract

The transcriptional coactivator with PDZ-binding motif (TAZ) is one of the important downstream effectors of Hippo pathway. In this study, the potential implication of TAZ in gliomagenesis was explored. TAZ expression was identified to be upregulated in glioma specimens and positively correlated with tumor grade. Meanwhile, its expression in nucleus was increased more significantly with the ascending order of tumor grade. Knocking down TAZ inhibited glioma cell proliferation, invasion and promoted apoptosis. Conversely, enforced upregulation of TAZ promoted proliferation, invasion of glioma cells, and suppressed apoptosis in vitro. When orthotopic glioblastoma mouse model implanted with TAZ knocked down cells, glioma growth was inhibited and survival period was prolonged. Expression of Ki67, MMP-9, Cyclin D1, Bcl-2 and C-myc was varied in accordance with the level of TAZ in glioma cell. The biomarkers of EMT (epithelial-mesenchymal transition), vimentin and N-cadherin, were downregulated when TAZ was suppressed. Using Co-immunoprecipitation TAZ was identified to bind to TEAD4. Therefore, our findings indicate that TAZ is overexpressed in glioma and translocated more into nucleus in high grade glioma. TAZ is involved in gliomagenesis by promoting glioma growth and may benefit to EMT progression. This result suggests that TAZ serves as a potential target for the treatment of glioma.

Induction of store-operated calcium entry (SOCE) suppresses glioblastoma growth by inhibiting the Hippo pathway transcriptional coactivators YAP/TAZ

“…To identify methods of inhibiting GBM growth, we carried out a small molecule screen using a library containing 1650 compounds, most of which are FDA-approved drugs. Our screen used LN229 human GBM cell line, which shows increased expression of TAZ 19 , presumably due to gene amplification (TCGA database). We confirmed that TAZ is essential for cell growth and tumorigenesis of LN229 cells by shRNA-mediated knockdown of TAZ in these cells (Figure S1A-S1F).…”

A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation

“…In addition, YAP/TAZ and β-catenin/TCF/LEF have been shown to work together in regulating target gene induction in the developing heart [48]. Although this has not been demonstrated in brain cancer, YAP and TAZ are frequently upregulated in glioma [49,50], and studies have shown that TAZ is required for the FZD7-induced proliferation of glioma cells [51], while TAZ inhibition leads to senescence and growth arrest [52].…”

The emerging role of Hippo signaling pathway in regulating osteoclast formation

“…The anti‐apoptotic molecule Bcl‐2 regulates the differentiation, activation, and survival of both osteoblasts and osteoclasts (Nagase et al, ). Expression of Bcl‐2 varied proportionally with the level of TAZ in glioma cells (Li et al, ). Induced overexpression of TAZ was able to increase Bcl‐2 expression and decrease expression of the Bcl‐2 associated X protein (Wang et al, ).…”