Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, People's Republic of China.
Cancer Institute, Fudan University Cancer Hospital and Cancer Metabolism Laboratory, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, People's Republic of China.
Biochem Biophys Res Commun. 2018 Sep 18;503(4):2240-2247. doi: 10.1016/j.bbrc.2018.06.144. Epub 2018 Jun 30.
The Hippo pathway is crucial in organ size control, and its dysregulation contributes to tumorigenesis. TAZ is an essential molecule containing a WW domain in Hippo pathway and serves as transcription co-activator to modulate cell proliferation and induce epithelial-mesenchymal transition in different human cancers, including pancreatic adenocarcinoma. In this study, we found that TAZ, a deletion occurred at its transactivation domain, increases phosphorylation at TAZ Ser89, resulting in sequestration of TAZ in cytoplasm and inhibiting its transcriptional activity. Furthermore, ectopic expression of TAZ promotes mesenchymal-epithelial transition (MET), demonstrating that Q233 is an essential site to control TAZ function. Our results disclose that TAZ plays a major role in regulating malignancy of cancer cells by hijacking Hippo pathway.
Hippo 通路在器官大小控制中至关重要，其失调会导致肿瘤发生。TAZ 是 Hippo 通路中的一个必需分子，含有一个 WW 结构域，作为转录共激活因子，在不同的人类癌症中调节细胞增殖并诱导上皮-间充质转化，包括胰腺腺癌。在这项研究中，我们发现 TAZ 的一个缺失发生在其转录激活域，导致 TAZ Ser89 的磷酸化增加，从而将 TAZ 隔离在细胞质中并抑制其转录活性。此外，TAZ 的异位表达促进了间充质-上皮转化（MET），表明 Q233 是控制 TAZ 功能的关键位点。我们的结果揭示了 TAZ 通过劫持 Hippo 通路在调节癌细胞恶性中的主要作用。
