TAZ is a novel oncogene in non-small cell lung cancer

Abstract

Transcriptional coactivator with PDZ-binding motif (TAZ) is a transcriptional coactivator involved in the differentiation of stem cell as well as the development of multiple organs. Recently, TAZ has also been identified as a major component of the novel Hippo-LATS tumor suppressor pathway and to function as an oncogene in breast cancer. We show for the first time that TAZ is an oncogene in non-small cell lung cancer (NSCLC). Our results show that TAZ is overexpressed in NSCLC cells and that lentivirus-mediated overexpression of TAZ in HBE135 immortalized human bronchial epithelial cells causes increased cell proliferation and transformation, which can be restored back to its original levels by knockdown of TAZ. In addition, short-hairpin RNA (shRNA)-mediated knockdown of TAZ expression in NSCLC cells suppresses their proliferation and anchorage-independent growth in vitro, and tumor growth in mice in vivo, which can be reversed by re-introduction of shRNA-resistant TAZ into TAZ-knockdown NSCLC cells. These results indicate that TAZ is an oncogene and has an important role in tumorigenicity of NSCLC cells. Therefore, TAZ may present a novel target for the future diagnosis, prognosis and therapy of lung cancer.

The N-terminal Phosphodegron Targets TAZ/WWTR1 Protein for SCFβ-TrCP-dependent Degradation in Response to Phosphatidylinositol 3-Kinase Inhibition

“…Notably, elevated TAZ expression is observed in more than 20% of breast cancers, especially invasive ductal carcinomas (15). TAZ is also implicated in papillary thyroid carcinoma and non-small cell lung cancer (19,20). Recently, studies have demonstrated that TAZ plays an important role in breast cancer stem cell self-renewal and mesenchymal differentiation in glioma (21,22).…”

YAP inhibits squamous transdifferentiation of Lkb1-deficient lung adenocarcinoma through ZEB2-dependent DNp63 repression

“…1f,g). TAZ, the YAP paralogue that shares many transcription factor targets with YAP, is previously shown to contribute to lung cancer progression and metastasis [22][23][24] . However, unlike YAP, TAZ expression showed no significant correlation with lung cancer pathologies ( Supplementary Fig.…”

The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation

“…Furthermore, genomic amplification and elevated expression and nuclear localization of YAP has been observed in human cancers (Overholtzer et al, 2006;Zender et al, 2006;Dong et al, 2007;Zhao et al, 2007;Steinhardt et al, 2008;Hall et al, 2010). Overexpression of TAZ has also been noted in human breast cancer samples and non-small cell lung cancer cell lines (Chan et al, 2008;Zhou et al, 2011b). Similar to YAP overexpression, ablation of the Hippo pathway components Mer and Sav and double knockout of Mst1/2 in mice result in liver enlargement and tumor formation characteristic of HCC and cholangiocarcinoma (CC) (Zhou et al, 2009;Benhamouche et al, 2010;Lee et al, 2010;Lu et al, 2010;Song et al, 2010;.…”