title: Hippo transducer TAZ promotes epithelial mesenchymal transition and supports pancreatic cancer progression.
abstract: 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.
authors.affiliation: Department of Oncology, Shanghai Tongji University Affiliated East Hospital, Shanghai, People's Republic of China.
authors.forename: Dacheng
authors.initials: D
authors.lastname: Xie
authors.affiliation: Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jiujie
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Gastroenterology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Tian
authors.initials: T
authors.lastname: Xia
authors.affiliation: Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Wenfei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Shanghai Tongji University Affiliated East Hospital, Shanghai, People's Republic of China.|Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Keping
authors.initials: K
authors.lastname: Xie
authors.affiliation: Department of Oncology, Shanghai Tongji University Affiliated East Hospital, Shanghai, People's Republic of China.|Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Quan
mesh_terms: D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D064593:Heterografts; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D014162:Transfection
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human
keywords: EMT; TAZ; metastasis; pancreatic cancer; proliferation