Truncated TEAD‐binding protein of TAZ inhibits glioma survival through the induction of apoptosis and repression of epithelial‐mesenchymal transition

Abstract

Transcriptional coactivator with PDZ‐binding motif (TAZ), a Hippo pathway downstream effector, promotes tumor progression by serving as a transcriptional coactivator with TEAD. Here, we introduced a new construct which can express the TEAD‐binding domain of TAZ protein (TAZBD), and determined its antitumor effect in malignant glioma both in vitro and in vivo. We first observed that TAZ was upregulated in glioma tissues and related to malignant clinicopathologic characteristic, indicating the crucial role of TAZ during glioma progression. In U87 and U251 cells, TAZBD expression increased the proportion of apoptotic cells, and suppressed the colony formation and tumorigenicity. Further, TAZBD also decreased cell metastasis through the repression of epithelial‐mesenchymal transition. The mechanistic study showed that TAZBD suppression of glioma cells was predominantly through blocking the TAZ‐TEAD complex formation by competing with endogenous TAZ. Thus, the gene therapy of malignant glioma through blocking TAZ‐TEAD complex by TAZBD may provide a new way for the targeted therapy of glioma.

YAP vs. TAZ: differences in expression revealed through rigorous validation of target-specific monoclonal antibodies

“…YAP and TAZ are both transcriptional co-activators, and both serve as key effector proteins in the Hippo signaling pathway [21][22][23][24] (Figure 1). Under growth-promoting conditions, YAP and TAZ have been reported to translocate from the cytoplasm to the nucleus where they interact with TEA-domain containing (TEAD) transcription factors to regulate the transcription of genes, many of which govern cell proliferation and apoptosis [24][25][26][27]. As such, YAP and TAZ have been strongly implicated in tissue growth, repair, and regeneration [28][29][30][31][32][33][34][35][36], and their dysregulation has been associated with tumor development in a variety of tissue types [22,25,37].…”