Hippo-YAP signaling pathway: A new paradigm for cancer therapy.
TLDR
This review chronicles the recent progress in elucidating the function of Hippo signaling in tumorigenesis and provide a rich source of potential targets for cancer therapy.Abstract:
In the past decades, the Hippo signaling pathway has been delineated and shown to play multiple roles in the control of organ size in both Drosophila and mammals. In mammals, the Hippo pathway is a kinase cascade leading from Mst1/2 to YAP and its paralog TAZ. Several studies have demonstrated that YAP/TAZ is a candidate oncogene and that other members of the Hippo pathway are tumor suppressive genes. The dysregulation of the Hippo pathway has been observed in a variety of cancers. This review chronicles the recent progress in elucidating the function of Hippo signaling in tumorigenesis and provide a rich source of potential targets for cancer therapy.read more
Citations
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RASSF1A elicits apoptosis through an MST2 pathway directing proapoptotic transcription by the p73 tumor suppressor protein.
David Matallanas,David Romano,Karen Yee,Katrin Meissl,Lucia Kucerova,Daniela Piazzolla,Manuela Baccarini,J. Keith Vass,Walter Kolch,Eric O'Neill +9 more
TL;DR: It is shown that key steps in RASSF1A-induced apoptosis are the disruption of the inhibitory Raf1-MST2 complex by RASSf1A and the concomitant enhancement of MST2 interaction with its substrate, LATS1.
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Dysregulated YAP1/TAZ and TGF-β signaling mediate hepatocarcinogenesis in Mob1a/1b-deficient mice
Miki Nishio,Keishi Sugimachi,Hiroki Goto,Jia Wang,Takumi Morikawa,Yosuke Miyachi,Yusuke Takano,Hiroki Hikasa,Tohru Itoh,Satoshi O. Suzuki,Hiroki Kurihara,Shinichi Aishima,Andrew Leask,Takehiko Sasaki,Toru Nakano,Hiroshi Nishina,Yuji Nishikawa,Yoshitaka Sekido,Kazuwa Nakao,Kazuo Shin-ya,Koshi Mimori,Akira Suzuki +21 more
TL;DR: The demonstration that well-tolerated and already-approved antiparasitic drugs inhibit YAP1 signaling may point to a new route of treatment for liver cancer based on inhibition of MOB1-YAP1/TAZ and/or TGF-βs–SMADs signaling.
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The TEAD family and its oncogenic role in promoting tumorigenesis
TL;DR: 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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The Hippo Pathway and YAP/TAZ–TEAD Protein–Protein Interaction as Targets for Regenerative Medicine and Cancer Treatment
Matteo Santucci,Tatiana Vignudelli,Stefania Ferrari,Marco Mor,Laura Scalvini,Maria Laura Bolognesi,Elisa Uliassi,Maria Paola Costi +7 more
TL;DR: An overview of the Hippo pathway, the sequence and structural analysis of YAP/TAZ, the known pharmacological modulators of the pathway, especially those targeting YAP-TAZ-TEAD interaction are presented.
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YAP/TAZ Activation as a Target for Treating Metastatic Cancer.
TL;DR: Evidence strongly suggests that inappropriate YAP or TAZ activity plays a causal role in cancer, and that targeting aberrant YAP/TAZ activation is a promising strategy for the treatment of metastatic disease.
References
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Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control
Bin Zhao,Xiaomu Wei,Weiquan Li,Ryan S. Udan,Ryan S. Udan,Qian Yang,Joungmok Kim,Joungmok Kim,Joe Xie,Tsuneo Ikenoue,Jindan Yu,Li Li,Li Li,Pan Zheng,Keqiang Ye,Arul M. Chinnaiyan,Georg Halder,Georg Halder,Zhi Chun Lai,Kun-Liang Guan,Kun-Liang Guan +20 more
TL;DR: It is demonstrated that in mammalian cells, the transcription coactivator YAP (Yes-associated protein), is inhibited by cell density via the Hippo pathway, and YAP overexpression regulates gene expression in a manner opposite to cell density, and is able to overcome cell contact inhibition.
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TEAD mediates YAP-dependent gene induction and growth control
Bin Zhao,Xin Ye,Jindan Yu,Li Li,Li Li,Weiquan Li,Siming Li,Jianjun Yu,Jiandie D. Lin,Cun-Yu Wang,Arul M. Chinnaiyan,Zhi Chun Lai,Kun-Liang Guan +12 more
TL;DR: TEAD is revealed as a new component in the Hippo pathway playing essential roles in mediating biological functions of YAP, and is required for YAP-induced cell growth, oncogenic transformation, and epithelial-mesenchymal transition.
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Hyaluronan: from extracellular glue to pericellular cue
TL;DR: This work highlights a key role for interactions between hyaluronan and tumour cells in several aspects of malignancy and indicates the possibility of new therapeutic strategies.
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Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2
Guy A. Rouleau,P. Merel,Mohini Lutchman,Marc Sanson,Marc Sanson,Jessica Zucman,Claude Marineau,Khê Hoang-Xuan,S. Demczuk,Chantal Desmaze,Béatrice Plougastel,Stefan M. Pulst,Gilbert M. Lenoir,E. K. Bijlsma,Raimund Fashold,Jan P. Dumanski,Pieter J. de Jong,Dilys M. Parry,Roswell Eldrige,Alain Aurias,Olivier Delattre,Gilles Thomas +21 more
TL;DR: The deduced product has homology with proteins at the plasma membrane and cytoskeleton Interface, a previously unknown site of action of tumour suppressor genes in humans.
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Genetic and pharmacological disruption of the TEAD–YAP complex suppresses the oncogenic activity of YAP
Yi Liu-Chittenden,Bo Huang,Joong Sup Shim,Qian Chen,Se-Jin Lee,Robert A. Anders,Jun O. Liu,Duojia Pan +7 more
TL;DR: It is shown 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.