Two Harvard-led groups pull well-cited cancer papers for duplication

the-journal-of-clinical-investigationTwo sets of authors based largely at Harvard Medical School have each retracted a paper for duplication in the same journal.

Both papers — which are more than a decade old — were pulled in The Journal of Clinical Investigation on November 1 by their respective corresponding authors.

One paper’s last author told us it was difficult to identify how the duplications occurred since the study took place so long ago, but added that multiple experiments had corroborated the results.

Here’s the first retraction notice for “Complementary roles of IRS-1 and IRS-2 in the hepatic regulation of metabolism:”

At the request of the corresponding author, the JCI is retracting this article. The authors were recently made aware of duplicated bands in Figures 1B, 3C, and 4C. After an extensive internal review, it was discovered that these duplications were introduced during figure assembly. The authors have stated that experimental data generated in the lab from the same time period support the original conclusions of the study and that other studies have subsequently confirmed and extended the primary conclusions of the manuscript. However, in the interest of maintaining accuracy in the published scientific literature and because the initial figures were not up to the standards of the JCI, the authors wish to retract this article. The authors apologize for these errors.

The 2005 study has so far been cited 176 times, according to Clarivate Analytics’ Web of Science, formerly part of Thomson Reuters.  

The study’s last author, Carl Ronald Kahn, a prominent diabetes researcher and physician, told Retraction Watch:

…after an extensive internal review, it was discovered that duplications of autoradiograms of western blots were present in 3 panels in this paper.  Although it is difficult more than 10 years after the fact to determine exactly when or how these arose, they were apparently introduced during figure assembly.  Almost all of these were in panels representing western blots from control tissues.

Kahn added that the study was retracted

in the interest of maintaining accuracy in the published scientific literature and because the initial figures were not up to the standards of JCI…

The paper has been the subject of a PubPeer threadas have some of Kahn’s other papers. In one such thread about a 2006 study, an author responded to a commenter saying:

I have always trained my students and fellows and worked myself to uphold the highest level of scientific integrity, and to be respectful of the process and other scientists. There is no doubt that over a long career with hundreds of publications containing literally data from thousands of experiments, an occasional error in reporting an experiment will occur, but to the best of my knowledge, neither I nor any of my colleagues or trainees has ever committed intentional scientific fraud.

We’ve found six more corrections for Kahn and first author Cullen Taniguchi (five list Kahn as an author and three include Taniguchi) for image-related issues (1, 2, 3, 4, 5, 6). Taniguchi is now based at MD Anderson Cancer Center.

Here’s the other retraction notice:

At the request of the corresponding author, the JCI is retracting this article. The authors were recently apprised that portions of the p27 blot and cyclin D1 blot of Figure 5A in this publication were duplicated and used to represent different samples. The corresponding author has indicated that previous and subsequent experiments from his and other laboratories support the conclusions reported in Figure 5A; however, the original data are no longer available. No issues have been raised with regard to any of the other data in the paper.

This 2002 paper, “Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer,” has been cited 215 times since publication.

We’ve reached out to the study’s first author, Sabina Signoretti (based at Harvard), and its last author, Michele Pagano (from New York University School of Medicine). We’ll update the post if we hear back.

We’ve come across some corrections fixing various problems with figures for this set of authors — three list Signoretti, one for Pagano, and three for penultimate author Massimo Loda (1, 2, 3, 4, 5). 

Other papers co-authored by Pagano and Loda are being discussed on PubPeer.

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14 thoughts on “Two Harvard-led groups pull well-cited cancer papers for duplication”

  1. “After extensive review … they were apparently introduced during figure assembly.” How else could this have happened? Why did it take extensive review to come to this (non) conclusion?

  2. Second Cullen M Taniguchi, C Ronald Kahn retraction.
    This time 2016 retraction of a 2003 J Biol Chem paper.

    J Biol Chem. 2003 Aug 29;278(35):33377-83. Epub 2003 Jun 13.
    Bi-directional regulation of brown fat adipogenesis by the insulin receptor.
    Entingh AJ1, Taniguchi CM, Kahn CR.
    Author information
    1Department of Cellular and Molecular Physiology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, Massachusetts 02215, USA.

    2016 retraction notice.
    http://www.jbc.org/content/291/53/27434

  3. 2016 correction figures 1 6 and 7 of 2004 Cullen M Taniguchi, C Ronald Kahn (Harvard) J Biol Chem paper.

    J Biol Chem. 2004 Sep 3;279(36):38016-24. Epub 2004 Jul 7.
    Differential roles of the insulin and insulin-like growth factor-I (IGF-I) receptors in response to insulin and IGF-I.
    Entingh-Pearsall A1, Kahn CR.
    Author information
    1Department of Cellular and Molecular Physiology, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

    2016 Correction notice.
    http://www.jbc.org/content/291/42/22339.short

    “There were several errors in this paper that the authors wish to correct. In the corrected Fig. 1, the panel showing the IGF1KO cells has been deleted because it appears to be an incorrect image. As Fig. 2 contains three example clones of IGFRKO cell differentiation, the presence of the IGFRKO panel in Fig. 1, which was not referred to under the “Results,” was redundant. We have also added dashed lines to indicate that the image was a composite of different tissue culture dishes. In the experiments shown in Fig. 6, A and B, the samples were loaded sequentially on the same gel, and the same basal sample served as 0 nM ligand for both insulin and IGF-1 stimulation. To create the double panel figures used in the paper, therefore, the basal sample lane was duplicated and spliced next to the IGF-1 stimulated samples. To clarify the confusion that this has created, a vertical white line has been added to the corrected Fig. 6 to all of the IGF-1 panels to indicate that the unstimulated lane to the left of the line has been spliced in and is the same unstimulated sample as appears in the insulin panels. The experiments in Fig. 7, B and C, were performed in the same fashion as those in Fig. 6. Therefore, the basal lanes shown in the IGF-1-stimulated panels are the same as the insulin-stimulated panels. For clarification, vertical white lines have been added to these figures to indicate the area of vertical splicing. None of these clarifications has any effect on the results of the study or their interpretation.”

  4. Mol Cell. 2006 Aug 4;23(3):319-29.
    SCFbetaTrCP-mediated degradation of Claspin regulates recovery from the DNA replication checkpoint response.

    Peschiaroli A1, Dorrello NV, Guardavaccaro D, Venere M, Halazonetis T, Sherman NE, Pagano M.
    Author information
    1
    Department of Pathology, NYU Cancer Institute, New York University School of Medicine, MSB 599, New York, New York 10016, USA.

    https://pubpeer.com/publications/D348DCA95FEC3070C4193AA06D83C2#fb121274

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

    Figure 2A.
    http://i.imgur.com/I8AvMf3.jpg

    Figure 6A.
    http://i.imgur.com/Tba2fLM.jpg

  5. Nature. 2008 Mar 20;452(7185):365-9. doi: 10.1038/nature06641.
    Control of chromosome stability by the beta-TrCP-REST-Mad2 axis.
    Guardavaccaro D1, Frescas D, Dorrello NV, Peschiaroli A, Multani AS, Cardozo T, Lasorella A, Iavarone A, Chang S, Hernando E, Pagano M.
    Author information

    1
    Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 550 First Avenue, MSB 599, New York, New York 10016, USA.

    https://pubpeer.com/publications/18354482

    Figure 2e. http://i.imgur.com/3kQSp7k.jpg

  6. EMBO J. 2002 Sep 16;21(18):4875-84.
    Dual mode of degradation of Cdc25 A phosphatase.
    Maddalena Donzelli*,1, Massimo Squatrito1, Dvora Ganoth2, Avram Hershko2, Michele Pagano3 and Giulio F. Draetta1
    1 European Institute of Oncology, 435 Via Ripamonti, I‐20141, Milan, Italy
    2 Unit of Biochemistry, B. Rappaport Faculty of Medicine, Technion‐Israel Institute of Technology, Haifa, 31096, Israel
    3 Department of Pathology, MSB 599, New York University School of Medicine and NYU Cancer Institute, 550 First Avenue, New York, NY 10016, USA

    https://pubpeer.com/publications/12234927

    Figure 4A. http://i.imgur.com/6f4BAs2.png

  7. Science. 2007 May 11;316(5826):900-4. Epub 2007 Apr 26.
    SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins.
    Busino L1, Bassermann F, Maiolica A, Lee C, Nolan PM, Godinho SI, Draetta GF, Pagano M.
    Author information

    1
    Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 550 First Avenue, MSB 599, New York, NY 10016, USA.

    https://pubpeer.com/publications/17463251

    Figure S10. http://i.imgur.com/Wl3T42q.jpg

    Figure S6A. http://i.imgur.com/Mxw2Hjb.jpg

    Figures S4B and C. http://i.imgur.com/gqCr41k.jpg

    Figures S3B and S4B. http://i.imgur.com/NZ7ckbB.jpg

  8. Mol Cell. 2004 Oct 8;16(1):47-58.
    An Rb-Skp2-p27 pathway mediates acute cell cycle inhibition by Rb and is retained in a partial-penetrance Rb mutant.

    Peng Ji1, Hong Jiang1, Katya Rekhtman1, Joanna Bloom2, Marina Ichetovkin1, Michele Pagano2, Liang Zhu, 1,
    1 Department of Developmental and Molecular Biology, The Albert Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461 USA
    2 Department of Pathology and New York University Cancer Institute, New York University School of Medicine, New York, NY 10016 USA

    https://pubpeer.com/publications/3A0C2F972038026B44A513614A2A6A#fb121452

    Figure 6I. http://i.imgur.com/mk7IGTm.jpg

    1. You get the feeling that researchers at that time resented having to illustrate their claims with evidence in the form of the original immunoblots, which they regarded as a form of entertainment rather than as a vehicle for information. So they had no qualms about composing them by splicing together multiple copies of the same lane.
      This is meant as a general statement, not directed at the present authors.

      Please tell me that attitudes have changed.

  9. 2019 Expression concern for first author of 2nd retraction in this post.

    PLoS One. 2009 Jun 11;4(6):e5877. doi: 10.1371/journal.pone.0005877.
    p63 promotes cell survival through fatty acid synthase.
    Sabbisetti V1, Di Napoli A, Seeley A, Amato AM, O’Regan E, Ghebremichael M, Loda M, Signoretti S.
    Author information
    1
    Department of Pathology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

    2019 Expression of Concern.
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219869

    After publication, concerns were raised about several western blot results reported in this article [1].

    The β-actin panel in Fig 4 for iPrEC-Tp63 cells appears similar to the β-actin panel in Fig 5D for SCC9-Tp63, with different aspect ratio. The original blots supporting these figures are no longer available, and so the authors are unable to resolve the questions regarding these control blots.
    It appears as though the same β-actin panels are presented in Fig 2D and in S1 Fig for SCC9 cells, although the p63 data and experimental conditions are different. The authors provided available blots in support of FASN, p-Akt, and β-actin results shown in S1B Fig (S1 File), which clarify that the incorrect β-actin blot was included for this experiment in the published figure. The original blots underlying Fig 2D and the p63 blot in S1B Fig are no longer available.
    p63 and β-actin data were reported multiple times in the article:
    ○. p63 in Fig 1A, Fig 3B, and Fig 4 for SCC9 cells
    ○. β-actin panels in Fig 1A, Fig 3B for SCC9 cells
    ○. p63 and β-actin panels for SCC9-Tp63 and iPREC-Tp63 cell lines in Fig 3B and Fig 4
    The authors commented that they believe the western blots in Figs 1A, 3B and 4 were obtained by analyzing proteins from the same experiments, and that the p63 data were presented multiple times in the article to demonstrate that the changes in FASN, p-Akt and pS6 levels were observed in cells in which they had also documented knockdown of p63 expression. The original SCC9 blots for p63 in Figs 1A, 3B and 4 and for β-actin in Figs 1A and 3B are provided in S2 File. The underlying blots are no longer available for the SCC9 β-actin blot shown in Fig 4, for the other SCC9 experiments shown in these figures, or for the iPREC-Tp63 or SCC9-Tp63 experiments.
    The same p63 data are presented in Figs 3B and 4 for the SCC9 cell line, although the β-actin data are different. The authors commented that the β-actin blot shown for SCC9 cells in Figs 1A and 3B also applies to the p63 experiment in Fig 4. The original blots are not available to clarify whether the β-actin blot shown in Fig 4 is the matched loading control for Akt, p-Akt, and p-S6 blots shown in this figure.
    The authors are unable to confirm whether the β-actin blots shown in the article’s figures are matched loading controls obtained using the same protein samples as in the corresponding experimental panels.
    The PLOS ONE Editors post this Expression of Concern to notify readers of the unresolved issues pertaining to the control data reported in this article and the unavailability of primary data to support most of the western blot results.

    Reference
    1. Sabbisetti V, Di Napoli A, Seeley A, Amato AM, O’Regan E, Ghebremichael M, et al. (2009) p63 Promotes Cell Survival through Fatty Acid Synthase. PLoS ONE 4(6): e5877. https://doi.org/10.1371/journal.pone.0005877 pmid:19517019

  10. 2019 Editor’s for first author 2nd retraction in this post.

    Clin Cancer Res. 2010 Jul 15;16(14):3628-38. doi: 10.1158/1078-0432.CCR-09-3022. Epub 2010 Jul 6.
    The efficacy of the novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 compared with rapamycin in renal cell carcinoma.
    Cho DC1, Cohen MB, Panka DJ, Collins M, Ghebremichael M, Atkins MB, Signoretti S, Mier JW.
    Author information
    1
    Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.

    Pubpeer: https://pubpeer.com/publications/5EBF91A44DDB8B2DC9D08C835DCE7B

    2019 Editor’s Note.
    http://clincancerres.aacrjournals.org/content/25/13/4194

    The editors are publishing this note to alert readers to a concern about this article (1): Western blot similarities exist in Fig. 4A (C-Myc and Vinculin). The original gels are not available for review.

    Reference
    1.↵Cho DC, Cohen MB, Panka DJ, Collins M, Ghebremichael M, Atkins MB, et al. The efficacy of the novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 compared with rapamycin in renal cell carcinoma. Clin Cancer Res 2010;16:3628–38.

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