Abstract
YAP and TAZ are highly related transcriptional regulators pervasively activated in human malignancies. Recent work indicates that, remarkably, YAP/TAZ are essential for cancer initiation or growth of most solid tumors. Their activation induces cancer stem cell attributes, proliferation, chemoresistance, and metastasis. YAP/TAZ are sensors of the structural and mechanical features of the cell microenvironment. A number of cancer-associated extrinsic and intrinsic cues conspire to overrule the YAP-inhibiting microenvironment of normal tissues, including changes in mechanotransduction, inflammation, oncogenic signaling, and regulation of the Hippo pathway. Addiction to YAP/TAZ thus potentially represents a central cancer vulnerability that may be exploited therapeutically.
Copyright © 2016 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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Cell Proliferation
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Drug Resistance, Neoplasm
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Hippo Signaling Pathway
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Humans
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Intracellular Signaling Peptides and Proteins / metabolism*
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Mechanotransduction, Cellular
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Neoplasms / metabolism*
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Neoplasms / pathology*
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Neoplasms / therapy
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Neoplastic Stem Cells / metabolism
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Phosphoproteins / metabolism*
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Protein Serine-Threonine Kinases / metabolism
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Signal Transduction
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Trans-Activators
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Transcription Factors
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Transcriptional Coactivator with PDZ-Binding Motif Proteins
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Tumor Microenvironment
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YAP-Signaling Proteins
Substances
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Adaptor Proteins, Signal Transducing
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Intracellular Signaling Peptides and Proteins
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Phosphoproteins
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Trans-Activators
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Transcription Factors
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Transcriptional Coactivator with PDZ-Binding Motif Proteins
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WWTR1 protein, human
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YAP-Signaling Proteins
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YAP1 protein, human
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Protein Serine-Threonine Kinases