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.

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Signal transducer and activator of transcription-3 (Stat3) is activated by a number of receptor and nonreceptor tyrosine kinases, whereas a constitutively active form of Stat3 alone is sufficient to induce neoplastic transformation. In the present report, we show that Stat3 can also be activated through homophilic interactions by the epithelial (E)-cadherin. Indeed, by plating cells onto surfaces coated with fragments encompassing the two outermost domains of this cadherin, we clearly show that cadherin engagement can activate Stat3, even in the absence of direct cell-to-cell contact. Most importantly, our results also reveal for the first time an unexpected and dramatic surge in total Rac1 and Cdc42 protein levels triggered by cadherin engagement and an increase in Rac1 and Cdc42 activity, which is responsible for the Stat3 stimulation observed. Inhibition of cadherin interactions using a peptide, a soluble cadherin fragment, or genetic ablation induced apoptosis, points to a significant role of this pathway in cell survival signaling, a finding that could also have important therapeutic implications.