Hippo transducer TAZ promotes epithelial mesenchymal transition and supports pancreatic cancer progression
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Dacheng Xie1, Jiujie Cui2, Tian Xia2,3, Zhiliang Jia2, Liang Wang2, Wenfei Wei2, Anna Zhu2, Yong Gao1,2, Keping Xie2 and Ming Quan1,2
1 Department of Oncology, Shanghai Tongji University Affiliated East Hospital, Shanghai, People’s Republic of China
2 Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
3 Department of Gastroenterology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China
Ming Quan, email:
Keping Xie, email:
Keywords: TAZ, EMT, proliferation, metastasis, pancreatic cancer
Received: August 10, 2015 Accepted: September 12, 2015 Published: September 21, 2015
Transcriptional co-activator with PDZ binding motif (TAZ) is a transducer of the Hippo pathway and promotes cancer development and progression. In the present study, we sought to determine the roles and underlying mechanisms of elevated expression and activation of TAZ in pancreatic cancer development and progression. The mechanistic role of TAZ and Hippo signaling in promotion of pancreatic cancer development and progression was examined using cell culture, molecular biology, and mouse models. The relevance of our experimental and mechanistic findings was validated using human pancreatic tumor specimens. We found that TAZ expression was markedly higher in pancreatic tumors than in normal pancreatic tissue. Further analysis of the correlation of TAZ expression with tissue microarray clinicopathologic parameters revealed that this expression was positively associated with tumor differentiation. Also, TAZ expression was higher in pancreatic cancer cell lines than in pancreatic ductal epithelial cells. TAZ activation in pancreatic cancer cells promoted their proliferation, migration, invasion, and epithelial-mesenchymal transition. Further mechanistic studies demonstrated that aberrant expression and activation of TAZ in pancreatic cancer cells resulted from suppression of the expression of Merlin, a positive regulator upstream of the Hippo pathway, and that the oncogenic function of TAZ in pancreatic cancer cells was mediated by TEA/ATTS domain transcription factors. Therefore, TAZ functioned as an oncogene and promoted pancreatic cancer epithelial-mesenchymal transition and progression. TAZ thus may be a target for effective therapeutic strategies for pancreatic cancer.
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