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      The TEAD Family and Its Oncogenic Role in Promoting Tumorigenesis


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          The TEAD family of transcription factors is necessary for developmental processes. The family members contain a TEA domain for the binding with DNA elements and a transactivation domain for the interaction with transcription coactivators. TEAD proteins are required for the participation of coactivators to transmit the signal of pathways for the downstream signaling processes. TEADs also play an important role in tumor initiation and facilitate cancer progression via activating a series of progression-inducing genes, such as CTGF, Cyr61, Myc and Gli2. Recent studies have highlighted that TEADs, together with their coactivators, promote or even act as the crucial parts in the development of various malignancies, such as liver, ovarian, breast and prostate cancers. Furthermore, TEADs are proposed to be useful prognostic biomarkers due to the ideal correlation between high expression and clinicopathological parameters in gastric, breast, ovarian and prostate cancers. In this review, we summarize the functional role of TEAD proteins in tumorigenesis and discuss the key role of TEAD transcription factors in the linking of signal cascade transductions. Improved knowledge of the TEAD proteins will be helpful for deep understanding of the molecular mechanisms of tumorigenesis and identifying ideal predictive or prognostic biomarkers, even providing clinical translation for anticancer therapy in human cancers.

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          Most cited references83

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          Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP.

          The Drosophila TEAD ortholog Scalloped is required for Yki-mediated overgrowth but is largely dispensable for normal tissue growth, suggesting that its mammalian counterpart may be exploited for selective inhibition of oncogenic growth driven by YAP hyperactivation. Here we test this hypothesis genetically and pharmacologically. We show that a dominant-negative TEAD molecule does not perturb normal liver growth but potently suppresses hepatomegaly/tumorigenesis resulting from YAP overexpression or Neurofibromin 2 (NF2)/Merlin inactivation. We further identify verteporfin as a small molecule that inhibits TEAD-YAP association and YAP-induced liver overgrowth. These findings provide proof of principle that inhibiting TEAD-YAP interactions is a pharmacologically viable strategy against the YAP oncoprotein.
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            Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach.

            The heterogeneity and instability of human tumors hamper straightforward identification of cancer-causing mutations through genomic approaches alone. Herein we describe a mouse model of liver cancer initiated from progenitor cells harboring defined cancer-predisposing lesions. Genome-wide analyses of tumors in this mouse model and in human hepatocellular carcinomas revealed a recurrent amplification at mouse chromosome 9qA1, the syntenic region of human chromosome 11q22. Gene-expression analyses delineated cIAP1, a known inhibitor of apoptosis, and Yap, a transcription factor, as candidate oncogenes in the amplicon. In the genetic context of their amplification, both cIAP1 and Yap accelerated tumorigenesis and were required to sustain rapid growth of amplicon-containing tumors. Furthermore, cIAP1 and Yap cooperated to promote tumorigenesis. Our results establish a tractable model of liver cancer, identify two oncogenes that cooperate by virtue of their coamplification in the same genomic locus, and suggest an efficient strategy for the annotation of human cancer genes.
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              The Hippo signaling pathway in stem cell biology and cancer.

              The Hippo signaling pathway, consisting of a highly conserved kinase cascade (MST and Lats) and downstream transcription coactivators (YAP and TAZ), plays a key role in tissue homeostasis and organ size control by regulating tissue-specific stem cells. Moreover, this pathway plays a prominent role in tissue repair and regeneration. Dysregulation of the Hippo pathway is associated with cancer development. Recent studies have revealed a complex network of upstream inputs, including cell density, mechanical sensation, and G-protein-coupled receptor (GPCR) signaling, that modulate Hippo pathway activity. This review focuses on the role of the Hippo pathway in stem cell biology and its potential implications in tissue homeostasis and cancer.

                Author and article information

                Role: Academic Editor
                Int J Mol Sci
                Int J Mol Sci
                International Journal of Molecular Sciences
                21 January 2016
                January 2016
                : 17
                : 1
                : 138
                [1 ]Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; zyhjoe@ 123456gmail.com (Y.Z.); huangtingting0531@ 123456gmail.com (T.H.)
                [2 ]Institute of Digestive Disease, Partner State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China; alfredcheng@ 123456cuhk.edu.hk (A.S.L.C.); junyu@ 123456cuhk.edu.hk (J.Y.)
                [3 ]Li Ka Shing Institute of Health Science, Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong, China
                [4 ]Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518000, China
                [5 ]School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
                [6 ]Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
                Author notes
                [* ]Correspondence: weikang@ 123456cuhk.edu.hk (W.K.); kfto@ 123456cuhk.edu.hk (K.F.T.); Tel.: +852-2632-1136 (W.K. & K.F.T.)

                These authors contributed equally to this work.

                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                : 09 December 2015
                : 15 January 2016

                Molecular biology
                tead proteins,transcription factor,hippo pathway,yap,taz,vgll
                Molecular biology
                tead proteins, transcription factor, hippo pathway, yap, taz, vgll


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