The official journal of INTERNATIONAL FEDERATION OF PIGMENT CELL SOCIETIES · SOCIETY FOR MELANOMA RESEARCH
PIGMENT CELL & MELANOMA Research In melanoma, Hippo signaling is affected by copy number alterations and YAP1 overexpression impairs patient survival
Moritz Menzel, Diana Meckbach, Benjamin Weide, Nora C. Toussaint, Karin Schilbach, Seema Noor, Thomas Eigentler, Kristian Ikenberg, Christian Busch, Leticia Quintanilla-Martinez, Ursula Kohlhofer, Antonia Göke, Friederike Göke, Rupert Handgretinger, Christian Ottmann, Boris C. Bastian, Claus Garbe, Martin Röcken, Sven Perner, Oliver Kohlbacher and Jürgen Bauer
DOI: 10.1111/pcmr.12249 Volume 27, Issue 4, Pages 671–673 If you wish to order reprints of this article, please see the guidelines here Supporting Information for this article is freely available here EMAIL ALERTS Receive free email alerts and stay up-to-date on what is published in Pigment Cell & Melanoma Research – click here
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Subscribe to PCMR and stay up-to-date with the only journal committed to publishing basic research in melanoma and pigment cell biology As a member of the IFPCS or the SMR you automatically get online access to PCMR. Sign up as a member today at www.ifpcs.org or at www.societymelanomaresarch.org
To take out a personal subscription, please click here More information about Pigment Cell & Melanoma Research at www.pigment.org
Pigment Cell Melanoma Res. 27; 671–673
LETTER TO THE EDITOR
In melanoma, Hippo signaling is affected by copy number alterations and YAP1 overexpression impairs patient survival Moritz Menzel1,*, Diana Meckbach1,*, Benjamin Weide1, Nora C. Toussaint2,9, Karin Schilbach3, Seema Noor1, Thomas Eigentler1, Kristian Ikenberg4, Christian Busch1, Leticia Quintanilla-Martinez5, € ke6, Friederike Go € ke6, Ursula Kohlhofer5, Antonia Go 3 7 Rupert Handgretinger , Christian Ottmann , Boris C. € cken1, Bastian8, Claus Garbe1, Martin Ro 5 2 € rgen Bauer1 Sven Perner , Oliver Kohlbacher and Ju 1 Department of Dermatology, University of T€ubingen, T€ubingen, Germany 2 Applied Bioinformatics, Center for Bioinformatics, University of T€ubingen, T€ubingen, Germany 3 Childrens Hospital, Department of Hematology and Oncology, University of T€ubingen, T€ubingen, Germany 4 Institute of Surgical Pathology, University Hospital Z€urich, Z€urich, Switzerland 5 Department of Pathology, University of T€ubingen, T€ubingen, Germany 6 Department of Prostate Cancer Research, Institute of Pathology, University of Bonn, Germany, 7 Chemical Genomics Centre of the Max Planck Society, Dortmund, Germany 8 Departments of Dermatology and Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA 9 Present address: New York Genome Center, New York, NY, USA CORRESPONDENCE J€ urgen Bauer, e-mail: [email protected] *These authors contributed equally to this work.
doi: 10.1111/pcmr.12249
Dear Editor, Melanoma cells have high metastatic potential. While various genes promoting malignant transformation of melanocytes have been discovered, few genes are known that directly affect melanoma invasion and metastasis (Gupta et al., 2005; Scott et al., 2011). Recently, it was demonstrated that YAP1 is involved in melanoma invasion (Nallet-Staub et al., 2014). YAP1 is an evolutionary conserved transcription cofactor of the Hippo pathway (Pan, 2010), which regulates cell proliferation and differentiation as well as organ size (Camargo et al., 2007; Dong et al., 2007; Zhang et al., 2011). Hippo signaling leads to phosphorylation and inactivation of YAP1. Increased copy number of YAP1 has been found in murine liver and breast tumor models (Overholtzer et al., 2006; Zender et al., 2006). YAP1 overexpression has been observed in several human cancers and has been associated with poor outcome (Hall et al., 2010; Kang et al., 2007). Nallet-Staub et al. showed for melanoma cell lines that YAP1 knockdown reduces while overexpression increases anchorage-independent growth and invasion. Metastasis to the lung ª 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
following tail vein injection in mice is reduced after YAP1 knockdown (Nallet-Staub et al., 2014). We could confirm this influence of YAP1 expression on the invasive and metastatic capacity of melanoma cells in additional melanoma cell lines using Matrigel invasion assay and subcutaneous injection of melanoma cells in immunodeficient NSG mice after lentiviral overexpression and knockdown of YAP1 (Figures S1 and S2). To explore potential mechanisms of YAP1 activation in melanoma, we searched the comparative genomic hybridization (CGH) data of 48 human primary melanomas and 10 melanoma metastases for YAP1 amplifications. We found narrow (
PIGMENT CELL & MELANOMA Research In melanoma, Hippo signaling is affected by copy number alterations and YAP1 overexpression impairs patient survival
Moritz Menzel, Diana Meckbach, Benjamin Weide, Nora C. Toussaint, Karin Schilbach, Seema Noor, Thomas Eigentler, Kristian Ikenberg, Christian Busch, Leticia Quintanilla-Martinez, Ursula Kohlhofer, Antonia Göke, Friederike Göke, Rupert Handgretinger, Christian Ottmann, Boris C. Bastian, Claus Garbe, Martin Röcken, Sven Perner, Oliver Kohlbacher and Jürgen Bauer
DOI: 10.1111/pcmr.12249 Volume 27, Issue 4, Pages 671–673 If you wish to order reprints of this article, please see the guidelines here Supporting Information for this article is freely available here EMAIL ALERTS Receive free email alerts and stay up-to-date on what is published in Pigment Cell & Melanoma Research – click here
Submit your next paper to PCMR online at http://mc.manuscriptcentral.com/pcmr
Subscribe to PCMR and stay up-to-date with the only journal committed to publishing basic research in melanoma and pigment cell biology As a member of the IFPCS or the SMR you automatically get online access to PCMR. Sign up as a member today at www.ifpcs.org or at www.societymelanomaresarch.org
To take out a personal subscription, please click here More information about Pigment Cell & Melanoma Research at www.pigment.org
Pigment Cell Melanoma Res. 27; 671–673
LETTER TO THE EDITOR
In melanoma, Hippo signaling is affected by copy number alterations and YAP1 overexpression impairs patient survival Moritz Menzel1,*, Diana Meckbach1,*, Benjamin Weide1, Nora C. Toussaint2,9, Karin Schilbach3, Seema Noor1, Thomas Eigentler1, Kristian Ikenberg4, Christian Busch1, Leticia Quintanilla-Martinez5, € ke6, Friederike Go € ke6, Ursula Kohlhofer5, Antonia Go 3 7 Rupert Handgretinger , Christian Ottmann , Boris C. € cken1, Bastian8, Claus Garbe1, Martin Ro 5 2 € rgen Bauer1 Sven Perner , Oliver Kohlbacher and Ju 1 Department of Dermatology, University of T€ubingen, T€ubingen, Germany 2 Applied Bioinformatics, Center for Bioinformatics, University of T€ubingen, T€ubingen, Germany 3 Childrens Hospital, Department of Hematology and Oncology, University of T€ubingen, T€ubingen, Germany 4 Institute of Surgical Pathology, University Hospital Z€urich, Z€urich, Switzerland 5 Department of Pathology, University of T€ubingen, T€ubingen, Germany 6 Department of Prostate Cancer Research, Institute of Pathology, University of Bonn, Germany, 7 Chemical Genomics Centre of the Max Planck Society, Dortmund, Germany 8 Departments of Dermatology and Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA 9 Present address: New York Genome Center, New York, NY, USA CORRESPONDENCE J€ urgen Bauer, e-mail: [email protected] *These authors contributed equally to this work.
doi: 10.1111/pcmr.12249
Dear Editor, Melanoma cells have high metastatic potential. While various genes promoting malignant transformation of melanocytes have been discovered, few genes are known that directly affect melanoma invasion and metastasis (Gupta et al., 2005; Scott et al., 2011). Recently, it was demonstrated that YAP1 is involved in melanoma invasion (Nallet-Staub et al., 2014). YAP1 is an evolutionary conserved transcription cofactor of the Hippo pathway (Pan, 2010), which regulates cell proliferation and differentiation as well as organ size (Camargo et al., 2007; Dong et al., 2007; Zhang et al., 2011). Hippo signaling leads to phosphorylation and inactivation of YAP1. Increased copy number of YAP1 has been found in murine liver and breast tumor models (Overholtzer et al., 2006; Zender et al., 2006). YAP1 overexpression has been observed in several human cancers and has been associated with poor outcome (Hall et al., 2010; Kang et al., 2007). Nallet-Staub et al. showed for melanoma cell lines that YAP1 knockdown reduces while overexpression increases anchorage-independent growth and invasion. Metastasis to the lung ª 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
following tail vein injection in mice is reduced after YAP1 knockdown (Nallet-Staub et al., 2014). We could confirm this influence of YAP1 expression on the invasive and metastatic capacity of melanoma cells in additional melanoma cell lines using Matrigel invasion assay and subcutaneous injection of melanoma cells in immunodeficient NSG mice after lentiviral overexpression and knockdown of YAP1 (Figures S1 and S2). To explore potential mechanisms of YAP1 activation in melanoma, we searched the comparative genomic hybridization (CGH) data of 48 human primary melanomas and 10 melanoma metastases for YAP1 amplifications. We found narrow (
