Retraction Watch

Tracking retractions as a window into the scientific process

Authors pull Mol Cell paper for “inappropriate manipulation” of data

with 17 comments

Molecular CellThe authors of a Molecular Cell paper have retracted it due to issues with multiple figures — including one with evidence of “intentional misconduct.”

According to the authors’ institution, IMIM in Barcelona, all co-authors are aware of the retraction. The penultimate author — Antonio García de Herrerosretracted three papers in May from the Journal of Biological Chemistry for reusing images to represent different experiments, and recently corrected multiple figures in a Journal of Cell Science paper over “possible duplications and/or splices.”

Here’s the newest retraction notice:

This article has been retracted at the request of the authors.

We, the authors, are retracting this article because of inappropriate manipulation of the data in the H3K4me3 blot in the left panel of Figure 3C (LOXL2). Specifically, a duplicated/inverted lane 3 replaced the original lane 1. Readers raised concerns about data presented in Figures 1, 3, and 4. We provided all of the raw data corresponding to these figures to Molecular Cell and the Scientific Integrity Committee of our institute, the IMIM (Hospital del Mar Medical Research Institute). The journal and the Scientific Integrity Committee of the IMIM found several issues, but determined that apart from the instance in Figure 3C, there was no evidence of intentional misconduct. However, because the data in the H3K4me3 blot in the left (LOXL2) panel of Figure 3C were inappropriately manipulated, resulting in a figure that does not accurately represent the data as obtained, we are retracting the paper. We wish to note that other experimental replicates reproduced the result in the H3K4me3 blot in Figure 3C’s left (LOXL2) panel. In addition, our subsequent papers showing that oxidation of H3 by LOXL2 has a central role in EMT (Millanes-Romero et al., Mol. Cell 2013) and that LOXL2 oxidizes methylated TAF10 (Iturbide et al., Mol. Cell 2015) support the central findings of this paper. We apologize to the scientific community for any inconveniences resulting from the publication and retraction of this manuscript.

The 2012 paper, “Lysyl Oxidase-like 2 Deaminates Lysine 4 in Histone H3,” has so far been cited 46 times, according to Thomson Reuters Web of Science.  

Rafael de la Torre Fornell, director of the Hospital del Mar Medical Research Institute (IMIM) in Barcelona, Spain, told us:

The editor of the journal contacted us several months ago and asked our institution to perform an inquiry on comments appeared in PubPeer regarding the article concerned. We performed an internal inquiry and an external expert was also requested to review those aspects of the manuscript under examination. We prepared a report with all materials collected that was submitted to the journal. On that basis, decisions were taken by the editorial board of the journal and elements of the report are present in the retraction of the manuscript.

Here’s the PubPeer thread to which Fornell referred.

Fornell added:

The senior author takes full responsibility of the manuscript. All authors are aware that the notice of the retraction has been issued. The Commission on Scientific Integrity of our institute will meet the next days and this retraction case will be reviewed and it will discussed if any corrective active action has to be taken.

When we reported on the case earlier this month, Fornell told us:

We are aware of retractions concerning Dr. Antonio Garcia-Herreros work. Internally this issue is managed by our Good Scientific Practices and Scientific Misconduct Committee. We are expecting the report of the committee to proceed with corrective actions.

Two of coauthor Víctor M. Díaz’s papers are being questioned on PubPeer, as is one paper by last author Sandra Peiró.

We’ve reached out to Peiró, and will update the post with anything else we learn.

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Written by Dalmeet Singh Chawla

June 29th, 2016 at 9:30 am

Comments
  • fernandopessoa June 29, 2016 at 10:00 am

    2015 paper (third) by Victor M Díaz being questioned at Pubpeer.

    Mol Cell Biol. 2015 Dec 28;36(6):923-40. doi: 10.1128/MCB.01074-15.
    A Switch in Akt Isoforms Is Required for Notch-Induced Snail1 Expression and Protection from Cell Death.
    Frías A1, Lambies G2, Viñas-Castells R2, Martínez-Guillamon C2, Dave N2, García de Herreros A3, Díaz VM3.
    Author information
    1Programa de Recerca en Càncer, Institut Hospital del Mar d’Investigacions Mèdiques, Barcelona, Spain Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
    2Programa de Recerca en Càncer, Institut Hospital del Mar d’Investigacions Mèdiques, Barcelona, Spain.
    3Programa de Recerca en Càncer, Institut Hospital del Mar d’Investigacions Mèdiques, Barcelona, Spain Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain

    PMID:26711268

    https://pubpeer.com/publications/26711268

  • fernandopessoa June 29, 2016 at 10:04 am

    Sandra Peiró paper being quesitoned at Pubpeer.

    https://pubpeer.com/publications/24239292

    Mol Cell. 2013 Dec 12;52(5):746-57. doi: 10.1016/j.molcel.2013.10.015. Epub 2013 Nov 14.
    Regulation of heterochromatin transcription by Snail1/LOXL2 during epithelial-to-mesenchymal transition.
    Millanes-Romero A1, Herranz N2, Perrera V3, Iturbide A1, Loubat-Casanovas J1, Gil J2, Jenuwein T3, García de Herreros A4, Peiró S5.
    Author information
    1Programa de Recerca en Càncer, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.
    2Cell Proliferation Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, W12 0NN London, UK.
    3Max Planck Institute of Immunology and Epigenetics, 79108 Freiburg, Germany.
    4Programa de Recerca en Càncer, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain; Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
    5Programa de Recerca en Càncer, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.

  • fernandopessoa June 29, 2016 at 10:06 am

    Sandra Peiró paper being quesitoned at Pubpeer.

    https://pubpeer.com/publications/10982788

    J Biol Chem. 2000 Dec 1;275(48):37846-52.
    PC12 cells have caveolae that contain TrkA. Caveolae-disrupting drugs inhibit nerve growth factor-induced, but not epidermal growth factor-induced, MAPK phosphorylation.
    Peiró S1, Comella JX, Enrich C, Martín-Zanca D, Rocamora N.
    Author information
    1Departament de Biologia Cellular i Anatomia Patològica, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain.

  • Oliver C. Schultheiss June 29, 2016 at 2:30 pm

    So this is due to “inappropriate data manipulation”? Makes me wonder what appropriate data manipulation would be, then. The stuff you don’t get caught doing?

  • fernandopessoa July 2, 2016 at 6:14 am

    First author retracted paper Mol Cell 46,369-376, recipient EMBO fellowship 2012.
    http://csc.mrc.ac.uk/embo-fellowship/

    EMBO Fellowship
    18 June 2012 | Research News
    EMBO FellowshipNicolas Herranz earns international fellowship

    Five months after arriving at the CSC, Nicolas Herranz has been awarded a Long-Term Fellowship by the European Molecular Biology Organization (EMBO). Nicolas recently joined joined the Cell Proliferation group, and the award secures his scientific post at the CSC for a further two years.

    These highly prestigious fellowships support young scientists to pursue international research careers. Following an intensive selection process, awards are made on the basis of an applicant’s previous scientific achievements, the novelty of their proposed research, and the merits of the host laboratory.

    “I was delighted to receive this,” said Nicolas. “It’s a fantastic fellowship, and gives you independence and security.” Nicolas completed his PhD in Barcelona, working at the IMIM research institute. His previous research was centred on the role of various epigenetic factors in cancer development. In his words, “during my PhD, I was trying to characterise epigenetic regulators involved in the epithelial-to-mesenchymal transition (EMT)”. EMT is a process in which cells within a primary tumour are transformed to be able to migrate away from the tumour and invade other areas of the body, forming secondary tumours. Understanding this process could be key to controlling the spread of cancer cells around the body.

    “I was looking at the role of certain proteins in this process. First I looked at Polycomb proteins, and then the less well-known LOXL2. We tried to characterise its function, and found out that LOXL2 was affecting the methylation of histones.” Histone methylation is an important form of epigenetic regulation: DNA is wrapped around structural proteins called histones. The change of the methylation status of these proteins can completely alter genes’ expression.

    Since joining the CSC, Nicolas has been making full use of the resources here to both continue this work and expand his research to encompass new areas. “I am continuing the work from my PhD. I can take advantage of my expertise in that field, and now use the brilliant facilities here. But I’m also doing work related to the ongoing research in Jesus Gil’s lab, about senescence.” In addition, Nicolas is in the nascent stages of investigating how cancerous cells can corrupt surrounding cells. Tumours can build up a chemical communication network by secreting a complex concoction of molecules. This manipulates nearby cells to promote tumour development. Advancing our knowledge of how these secreted factors might play a role in cancer development could lead to important novel approaches to cancer therapy.

    Nicolas is enjoying the freedom of postdoctoral research. “When you do your PhD, everything has to be closely related, and contribute to your thesis. As a postdoc it’s different, and more about the results. I have many more options now.” Nicolas will officially begin his fellowship in February 2013.

    -AL

  • fernandopessoa July 2, 2016 at 8:33 am

    In the retraction notice: “In addition, our subsequent papers showing that oxidation of H3 by LOXL2 has a central role in EMT (Millanes-Romero et al., Mol. Cell 2013) and that LOXL2 oxidizes methylated TAF10 (Iturbide et al., Mol. Cell 2015) support the central findings of this paper.”

    Millanes-Romero et al., Mol. Cell 2013
    https://pubpeer.com/publications/24239292
    Figure 4C. http://i.imgur.com/ezP8ol5.jpg

  • fernandopessoa July 3, 2016 at 3:36 am

    Victor Manuel Díaz
    https://www.upf.edu/cexs/community/facult/diaz.html

    “Professional/academic positions
    2003-2006 Postdoctoral Marie Curie Research Fellow. DIBIT-Universita Vita-Salute San Raffaele Hospital, Milan, Italy”

    coauthor on this paper:

    Prep1 Deficiency Induces Protection from Diabetes and Increased Insulin Sensitivity through a p160-Mediated Mechanism▿
    Francesco Oriente1, Luis Cesar Fernandez Diaz3, Claudia Miele1, Salvatore Iovino1, Silvia Mori3, Victor Manuel Diaz4, Giancarlo Troncone2, Angela Cassese1, Pietro Formisano1, Francesco Blasi3,4 and Francesco Beguinot1,*
    – Author Affiliations
    1Dipartimento di Biologia e Patologia Cellulare e Molecolare & Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Università degli Studi di Napoli Federico II, Naples, Italy
    2Dipartimento di Scienze Biomorfologiche e Funzionali, Università degli Studi di Napoli Federico II, Naples, Italy
    3IFOM (FIRC Institute of Molecular Oncology), via Adamello 16, 20134 Milan, Italy
    4Università Vita Salute San Raffaele, via Olgettina 60, 20132 Milan, Italy.

    https://pubpeer.com/publications/18644868
    Figure 5C.
    http://i.imgur.com/7OWC16k.jpg
    Figure 6A.
    http://i.imgur.com/EM1WifR.jpg
    Figure 8A.
    http://i.imgur.com/M5rOkXy.jpg

    • fernandopessoa July 3, 2016 at 3:43 am

      Mol Cell Biol. 2008 Sep;28(18):5634-45.

  • fernandopessoa July 3, 2016 at 3:47 am

    Victor Manuel Díaz
    https://www.upf.edu/cexs/community/facult/diaz.html

    “Professional/academic positions
    2003-2006 Postdoctoral Marie Curie Research Fellow. DIBIT-Universita Vita-Salute San Raffaele Hospital, Milan, Italy”

    coauthor on this paper:

    Characterization of the regulatory region of the zebrafish Prep1.1 gene: analogies to the promoter of the human PREP1.
    Bernardi E, Deflorian G, Pezzimenti F, Diaz VM, Mione M, Blasi F.
    PLoS One. 2010 Dec 22;5(12):e15047. doi: 10.1371/journal.pone.0015047.
    Author information.
    Elisa Bernardi, Gianluca Deflorian, Federica Pezzinenti, Marina Mione, Francesco Blasi
    IFOM-FIRC Institute of Molecular Oncology Foundation, Milan, Italy
    Victor M. Diaz, Francesco Blasi
    Università Vita Salute San Raffaele, Milan, Italy

    https://pubpeer.com/publications/21203543

    Figure 1B.
    http://i.imgur.com/fYN0vg5.jpg

  • fernandopessoa July 3, 2016 at 3:55 am

    Victor M Díaz paper being questioned at Pubpeer.

    J Biol Chem. 2010 Feb 5;285(6):3794-805. doi: 10.1074/jbc.M109.065995. Epub 2009 Dec 2.
    The hypoxia-controlled FBXL14 ubiquitin ligase targets SNAIL1 for proteasome degradation.
    Viñas-Castells R1, Beltran M, Valls G, Gómez I, García JM, Montserrat-Sentís B, Baulida J, Bonilla F, de Herreros AG, Díaz VM.
    Author information
    1Programa de Recerca en Càncer, Institut Municipal d’Investigació Mèdica, Hospital del Mar, Parc de Recerca Biomèdica de Barcelona, Doctor Aiguader 88, E-08003 Barcelona, Spain.

    https://pubpeer.com/publications/19955572

    Figure 5D.
    http://i.imgur.com/wm6ZwDF.jpg

  • fernandopessoa July 6, 2016 at 3:31 am

    Antonio Garcia de Herreros coauthor on Endocr Relat Cancer. 2007 Mar;14(1):141-51.

    https://pubpeer.com/publications/17395983

    Figure 2B.
    http://i.imgur.com/By2qOIG.jpg

    Endocr Relat Cancer. 2007 Mar;14(1):141-51.
    The inhibition of Wnt/β-catenin signalling by 1α,25-dihydroxyvitamin D3 is abrogated by Snail1 in human colon cancer cells
    María Jesús Larriba, Noelia Valle, Héctor G Pálmer, Paloma Ordóñez-Morán, Silvia Álvarez-Díaz, Karl-Friedrich Becker1, Carlos Gamallo2, Antonio García de Herreros3, José Manuel González-Sancho and Alberto Muñoz
    – Author Affiliations

    Instituto de Investigaciones Biomédicas ‘Alberto Sols’, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Arturo Duperier 4, E-28029 Madrid, Spain
    1Institut für Pathologie, Technische Universität München, Trogerstrasse 18, D-81675 München, Germany
    2Hospital Universitario de la Princesa, Diego de León 62, E-28006 Madrid, Spain
    3Institut Municipal d’Investigació Mèdica-Universitat Pompeu-Fabra, Doctor Aiguader 80, E-08003 Barcelona, Spain

  • fernandopessoa July 6, 2016 at 3:35 am

    Antonio Garcia de Herreros coauthor on Cancer Res. 2005 Dec 15;65(24):11649-57.

    https://pubpeer.com/publications/16357176

    Figure 3D.
    http://i.imgur.com/mbKdrkX.jpg

    Cancer Res. 2005 Dec 15;65(24):11649-57.
    Endothelin-1 promotes epithelial-to-mesenchymal transition in human ovarian cancer cells.

    Laura Rosanò1, Francesca Spinella1, Valeriana Di Castro1, Maria Rita Nicotra2, Shoukat Dedhar3, Antonio Garcia de Herreros4, Pier Giorgio Natali1, and Anna Bagnato1
    1Laboratory of Molecular Pathology and Ultrastructure, Regina Elena Cancer Institute; 2Molecular Biology and Pathology Institute, National Research Council, Rome, Italy; 3British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada; and 4Unitat de Biologia Cellular i Molecular, Institut Municipal d’Investigació Mèdica, Universitat Pompeu Fabra, Barcelona, Spain

  • fernandopessoa July 6, 2016 at 6:07 am

    Antonio Garcia de Herreros coauthor on Oncogene. 2009 Dec 10;28(49):4375-85.

    Compare figure figure 4a Oncogene 28:4375(2009) (this paper) with figure 1 Gut 52: 1756 (2003). http://i.imgur.com/VrMEtUT.jpg

    https://pubpeer.com/publications/19802011

    For reference: Gut 52:1756.
    https://pubpeer.com/publications/03F0D154CB61EC29CC6C6845DFC724#fb38166

    Oncogene. 2009 Dec 10;28(49):4375-85. doi: 10.1038/onc.2009.285.
    SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue.
    C Peña1,7, J M García1,7, M J Larriba2, R Barderas3, I Gómez1, M Herrera1, V García1, J Silva1, G Domínguez1, R Rodríguez4, J Cuevas5, A G de Herreros6, J I Casal3, A Muñoz2 and F Bonilla1

    1Department of Medical Oncology, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, Spain
    2Instituto de Investigaciones Biomédicas ‘Alberto Sols’, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain
    3Functional Proteomics Laboratory, Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain
    4Department of Pathology, Hospital Virgen de la Salud, Toledo, Spain
    5Department of Pathology, Hospital General Universitario, Guadalajara, Spain
    6Unitat de Biología Cellular i Molecular, Institut Municipal d’Investigació Mèdica, Universitat Pompeu Fabra, Barcelona, Spain

  • fernandopessoa July 6, 2016 at 9:12 am

    Tesis doctoral=http://www.tdx.cat/bitstream/10803/80660/1/tnhm.pdf

  • fernandopessoa July 7, 2016 at 4:52 am

    http://imgur.com/AxizKG5

    Tesis doctoral Nicolas Herrnaz Martin 2011: http://www.tdx.cat/handle/10803/80660
    Tesis doctoral Ana Millanes Romero 2014: http://www.tdx.cat/handle/10803/129339

  • fernando pessoa November 19, 2016 at 10:59 am

    Many elements of Mol Cell 46:369 (published 2012 retracted 2016) have been published as part of FEBS J. 2016 Oct 13. doi: 10.1111/febs.

    Pubpeer comments comparing the 2 publications:
    https://pubpeer.com/publications/8A9B324060E1673639C5114CC0F3C5#fb111086

    FEBS J. 2016 Oct 13. doi: 10.1111/febs.13922. [Epub ahead of print]
    Lysyl oxidase-like 2 (LOXL2) oxidizes trimethylated lysine 4 in histone H3.
    Herranz N1, Dave N1, Millanes-Romero A1, Pascual-Reguant L1, Morey L2, Díaz VM1,3, Lórenz-Fonfría V4, Gutierrez-Gallego R3, Jerónimo C2, Iturbide A1, Di Croce L2,3,5, García de Herreros A1,3, Peiró S6.
    Author information
    1Programa de Recerca en Càncer, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain.
    2Centre de Regulació Genòmica (CRG), Barcelona, Spain.
    3Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
    4Unitat de Biofísica, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain.
    5Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.
    6Programa de Recerca en Càncer, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain.

    PMID: 27735137 DOI: 10.1111/febs.13922

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