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      TAZ Is Highly Expressed in Gastric Signet Ring Cell Carcinoma

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          Abstract

          Transcriptional coactivator with PDZ-binding motif ( TAZ) is known to bind to a variety of transcription factors to control cell differentiation and organ development. We examined TAZ protein levels in 146 stage II–IV gastric cancer using immunohistochemistry (IHC), while TAZ mRNA was confirmed by quantitative reverse-transcription polymerase chain reaction (QRT-PCR) in 84 samples with enough tissue. TAZ protein expression was positive in 113 out of 146 (77.4%) gastric cancer samples. In parallel, TAZ mRNA expression was successfully detected in 81 of the 84 (96.4%) samples. Protein levels of TAZ were positively correlated with its mRNA levels ( P = 0.018). High expression of TAZ protein was observed with higher percentage in gastric cancer samples with histology of signet ring cell carcinoma (SRCC) than adenocarcinoma (85.7% versus 60.2%, P = 0.001). Similarly, TAZ mRNA level was higher in SRCC than in adenocarcinoma ( P = 0.003). When correlated with survival, the median overall survival (OS) is 14 months (95% CI: 12.2–15.8 months) in all patients. There was no significant association between survival and other clinical characteristics or TAZ expression levels. Our results show that TAZ is highly expressed in SRCC. TAZ might be considered as a target for the treatment of gastric SRCC in future.

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            A role for TAZ in migration, invasion, and tumorigenesis of breast cancer cells.

            TAZ (WWTR1), identified as a 14-3-3 binding protein with a PDZ binding motif, modulates mesenchymal stem cell differentiation. We now show that TAZ plays a critical role in the migration, invasion, and tumorigenesis of breast cancer cells. TAZ is conspicuously expressed in human breast cancer cell lines in which its expression levels generally correlate with the invasiveness of cancer cells. Overexpression of TAZ in low-expressing MCF10A cells causes morphologic changes characteristic of cell transformation and promotes cell migration and invasion. Conversely, RNA interference-mediated knockdown of TAZ expression in MCF7 and Hs578T cells reduces cell migration and invasion. TAZ knockdown in MCF7 cells also retards anchorage-independent growth in soft agar and tumorigenesis in nude mice. Significantly, TAZ is overexpressed in approximately 20% of breast cancer samples. These results indicate that TAZ plays a role in the migration, invasion, and tumorigenesis of breast cancer cells and thus presents a novel target for the detection and treatment of breast cancer.
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              The transcriptional coactivator TAZ regulates mesenchymal differentiation in malignant glioma.

              Recent molecular classification of glioblastoma (GBM) has shown that patients with a mesenchymal (MES) gene expression signature exhibit poor overall survival and treatment resistance. Using regulatory network analysis of available expression microarray data sets of GBM, including The Cancer Genome Atlas (TCGA), we identified the transcriptional coactivator with PDZ-binding motif (TAZ), to be highly associated with the MES network. TAZ expression was lower in proneural (PN) GBMs and lower-grade gliomas, which correlated with CpG island hypermethylation of the TAZ promoter compared with MES GBMs. Silencing of TAZ in MES glioma stem cells (GSCs) decreased expression of MES markers, invasion, self-renewal, and tumor formation. Conversely, overexpression of TAZ in PN GSCs as well as murine neural stem cells (NSCs) induced MES marker expression and aberrant osteoblastic and chondrocytic differentiation in a TEAD-dependent fashion. Using chromatin immunoprecipitation (ChIP), we show that TAZ is directly recruited to a majority of MES gene promoters in a complex with TEAD2. The coexpression of TAZ, but not a mutated form of TAZ that lacks TEAD binding, with platelet-derived growth factor-B (PDGF-B) resulted in high-grade tumors with MES features in a murine model of glioma. Our studies uncover a direct role for TAZ and TEAD in driving the MES differentiation of malignant glioma. © 2011 by Cold Spring Harbor Laboratory Press
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                Author and article information

                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi Publishing Corporation
                2314-6133
                2314-6141
                2014
                24 February 2014
                : 2014
                : 393064
                Affiliations
                1The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, 321 Zhongshan Road, Nanjing 210008, China
                2Pangaea Biotech, USP Dexeus University Institute, Barcelona, Spain
                3Department of General Surgery, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
                Author notes

                Academic Editor: Koichi Handa

                Author information
                http://orcid.org/0000-0003-0817-3400
                Article
                10.1155/2014/393064
                3953576
                24707483
                30484cac-3508-44b7-af3f-5ac8122ce492
                Copyright © 2014 Guofeng Yue et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 November 2013
                : 7 January 2014
                : 17 January 2014
                Funding
                Funded by: http://dx.doi.org/10.13039/501100001809 National Natural Science Foundation of China
                Award ID: 81000980
                Funded by: http://dx.doi.org/10.13039/501100001809 National Natural Science Foundation of China
                Award ID: 81220108023
                Funded by: http://dx.doi.org/10.13039/501100001809 National Natural Science Foundation of China
                Award ID: 81370064
                Categories
                Research Article

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