Pro-Invasive Activity of the Hippo Pathway Effectors YAP and TAZ in Cutaneous Melanoma

YAP and its paralog protein TAZ are downstream effectors of the Hippo pathway. Both are amplified in many human cancers and promote cell proliferation and epithelial–mesenchymal transition. Little is known about the status of the Hippo pathway in cutaneous melanoma. We profiled Hippo pathway compone...

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Autores principales: Nallet-Staub, Flore, Marsaud, Véronique, Li, Ling, Gilbert, Cristèle, Dodier, Sophie, Bataille, Véronique, Sudol, Marius, Herlyn, Meenhard, Mauviel, Alain
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938155/
https://www.ncbi.nlm.nih.gov/pubmed/23897276
http://dx.doi.org/10.1038/jid.2013.319
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author Nallet-Staub, Flore
Marsaud, Véronique
Li, Ling
Gilbert, Cristèle
Dodier, Sophie
Bataille, Véronique
Sudol, Marius
Herlyn, Meenhard
Mauviel, Alain
author_facet Nallet-Staub, Flore
Marsaud, Véronique
Li, Ling
Gilbert, Cristèle
Dodier, Sophie
Bataille, Véronique
Sudol, Marius
Herlyn, Meenhard
Mauviel, Alain
author_sort Nallet-Staub, Flore
collection PubMed
description YAP and its paralog protein TAZ are downstream effectors of the Hippo pathway. Both are amplified in many human cancers and promote cell proliferation and epithelial–mesenchymal transition. Little is known about the status of the Hippo pathway in cutaneous melanoma. We profiled Hippo pathway component expression in a panel of human melanoma cell lines and melanocytic lesions, and characterized the capacity of YAP and TAZ to control melanoma cell behavior. YAP and TAZ immuno-staining in human samples revealed mixed cytoplasmic and nuclear staining for both proteins in benign nevi and superficial spreading melanoma. TAZ was expressed at higher levels than YAP1/2 in all cell lines and in those with high invasive potential. Stable YAP or TAZ knockdown dramatically reduced the expression of the classical Hippo target CCN2/connective-tissue growth factor (CTGF), as well as anchorage-independent growth, capacity to invade Matrigel, and ability form lung metastases in mice following tail-vein injection. YAP knockdown also reduced invasion in a model of skin reconstruct. Inversely, YAP overexpression increased melanoma cell invasiveness, associated with increased TEA domain–dependent transcription and CCN2/CTGF expression. Together, these results demonstrate that both YAP and TAZ contribute to the invasive and metastatic capacity of melanoma cells and may represent worthy targets for therapeutic intervention.
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spelling pubmed-39381552014-02-28 Pro-Invasive Activity of the Hippo Pathway Effectors YAP and TAZ in Cutaneous Melanoma Nallet-Staub, Flore Marsaud, Véronique Li, Ling Gilbert, Cristèle Dodier, Sophie Bataille, Véronique Sudol, Marius Herlyn, Meenhard Mauviel, Alain J Invest Dermatol Original Article YAP and its paralog protein TAZ are downstream effectors of the Hippo pathway. Both are amplified in many human cancers and promote cell proliferation and epithelial–mesenchymal transition. Little is known about the status of the Hippo pathway in cutaneous melanoma. We profiled Hippo pathway component expression in a panel of human melanoma cell lines and melanocytic lesions, and characterized the capacity of YAP and TAZ to control melanoma cell behavior. YAP and TAZ immuno-staining in human samples revealed mixed cytoplasmic and nuclear staining for both proteins in benign nevi and superficial spreading melanoma. TAZ was expressed at higher levels than YAP1/2 in all cell lines and in those with high invasive potential. Stable YAP or TAZ knockdown dramatically reduced the expression of the classical Hippo target CCN2/connective-tissue growth factor (CTGF), as well as anchorage-independent growth, capacity to invade Matrigel, and ability form lung metastases in mice following tail-vein injection. YAP knockdown also reduced invasion in a model of skin reconstruct. Inversely, YAP overexpression increased melanoma cell invasiveness, associated with increased TEA domain–dependent transcription and CCN2/CTGF expression. Together, these results demonstrate that both YAP and TAZ contribute to the invasive and metastatic capacity of melanoma cells and may represent worthy targets for therapeutic intervention. Nature Publishing Group 2014-01 2013-08-29 /pmc/articles/PMC3938155/ /pubmed/23897276 http://dx.doi.org/10.1038/jid.2013.319 Text en Copyright © 2014 The Society for Investigative Dermatology, Inc http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Nallet-Staub, Flore
Marsaud, Véronique
Li, Ling
Gilbert, Cristèle
Dodier, Sophie
Bataille, Véronique
Sudol, Marius
Herlyn, Meenhard
Mauviel, Alain
Pro-Invasive Activity of the Hippo Pathway Effectors YAP and TAZ in Cutaneous Melanoma
title Pro-Invasive Activity of the Hippo Pathway Effectors YAP and TAZ in Cutaneous Melanoma
title_full Pro-Invasive Activity of the Hippo Pathway Effectors YAP and TAZ in Cutaneous Melanoma
title_fullStr Pro-Invasive Activity of the Hippo Pathway Effectors YAP and TAZ in Cutaneous Melanoma
title_full_unstemmed Pro-Invasive Activity of the Hippo Pathway Effectors YAP and TAZ in Cutaneous Melanoma
title_short Pro-Invasive Activity of the Hippo Pathway Effectors YAP and TAZ in Cutaneous Melanoma
title_sort pro-invasive activity of the hippo pathway effectors yap and taz in cutaneous melanoma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938155/
https://www.ncbi.nlm.nih.gov/pubmed/23897276
http://dx.doi.org/10.1038/jid.2013.319
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