On April 17th, Mathieu Bollen, a researcher at KU Leuven in Belgium, received a notice from PubPeer: A paper he had published in 2013 appeared to have data duplications.
The article, “Maternal Embryonic Leucine Zipper Kinase (MELK) Reduces Replication Stress in Glioblastoma Cells,” published in the Journal of Biological Chemistry, offered an explanation for why elevated levels of the MELK protein are associated with growth of a particular kind of brain tumor, glioblastoma. Several clinical trials are investigating MELK inhibitors as cancer treatments.
Bollen, the paper’s corresponding author, told Retraction Watch that one instance of image duplication, the inclusion of a gel-band from an unrelated experiment to represent a control, was “worrisome” but easily explainable:
based upon the prompt feedback of the first author, we initially believed that this was due to a human error that could be rectified by publication of a correction.
But after taking a closer look, Bollen and his co-authors found three more “inconsistencies” in the data. He said they informed the journal and emailed the evidence of falsification to Cenk Kig, the first author, who was a postdoctoral researcher at the time the paper came out but left the lab in 2014.
Kig “immediately” confessed to data manipulation, Bollen said. The journal retracted the paper on July 7, with a notice that provides a bit of color on Kig’s confession:
Confronted with these findings, the first author declared randomly choosing some data during final figure assembly.
Bollen said that Kig agreed with the rest of the co-authors that that paper should be retracted. The paper has been cited 20 times, according to Clarivate Analytics’ Web of Science.
Kig’s Google Scholar profile says he’s a professor at the medical school of Yeni Yuzyil University in Istanbul, Turkey. KU Leuven confirmed that he no longer works at the university. Attempts to reach Kig at several email addresses have returned error messages. Turkey’s university system has been unstable following a politically-motivated purge of academics last year, although there’s nothing to indicate that Kig has been personally affected.
Inge Lerouge, of KU Leuven’s Research Coordination Office, told us that in June the university’s Commission on Research Integrity began a scientific misconduct investigation. She declined to offer more detail on its scope or status, citing confidentiality rules.
Bollen told us that although Kig admitted to doctoring the paper, the team is still at a loss as to why:
The first author did not provide a coherent explanation. None of the co-authors of the manuscript ever noted a problem of scientific integrity during their (numerous) discussions with the first author. Apparently, the first author felt some kind of pressure to manipulate his data at the time of manuscript preparation, but I have no real insights into the nature of this pressure.
Bollen said he and his other co-authors are now working to re-do the experiments to see if there’s any validity to the findings they reported. However, the PubPeer discussion on this paper was started because a recent paper, published March 24, 2017 in eLife, suggests that inhibiting the MELK protein does not slow down certain types of cancer.
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J Biol Chem. 2001 Jan 12;276(2):1361-8.
Structural and catalytic similarities between nucleotide pyrophosphatases/phosphodiesterases and alkaline phosphatases.
Gijsbers R1, Ceulemans H, Stalmans W, Bollen M.
Author information
1
Afdeling Biochemie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
https://pubpeer.com/publications/F30610EBFF549CD9E069CCEAF03187
figure 6A and 8.
Biochem J. 2004 Jul 1;381(Pt 1):71-7.
Substrate-specifying determinants of the nucleotide pyrophosphatases/phosphodiesterases NPP1 and NPP2.
Cimpean A1, Stefan C, Gijsbers R, Stalmans W, Bollen M.
Author information
1
Afdeling Biochemie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Herestraat 49, B-3000 Leuven, Belgium.
https://pubpeer.com/publications/487913865492CAA31EEDD28507A04E
Figures 6A and 7A.
FEBS Lett. 1999 Jul 16;455(1-2):175-8.
Identification of MYPT1 and NIPP1 as subunits of protein phosphatase 1 in rat liver cytosol.
Boudrez A1, Evens K, Beullens M, Waelkens E, Stalmans W, Bollen M.
Author information
1
Afdeling Biochemie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Louvain, Belgium.
https://pubpeer.com/publications/A52A582E4693E8B2DFDB8BD3364322
Compare figure 4 FEBS Lett 455:175 with figure 1 Biochim Biophys Acta 1450:45.
For reference Biochim Biophys Acta 1450:45.
https://pubpeer.com/publications/10231554
You are really good at this!
“Based on these preclinical results, the MELK inhibitor OTS167 is currently being tested as a novel chemotherapy agent in several clinical trials.”
I wonder what could possibly have made the first author feel some kind of pressure to manipulate his data?
J Cell Sci. 2005 Jul 15;118(Pt 14):3081-9. Epub 2005 Jun 28.
Proteolytic maturation and activation of autotaxin (NPP2), a secreted metastasis-enhancing lysophospholipase D.
Jansen S1, Stefan C, Creemers JW, Waelkens E, Van Eynde A, Stalmans W, Bollen M.
Author information
1
Division of Biochemistry, Flanders Interuniversity Institute for Biotechnology, Faculty of Medicine, K.U. Leuven, B-3000 Leuven, Belgium.
https://pubpeer.com/publications/A0933611692B9A9979CEDA00CC2943
FEBS Lett. 2003 Mar 13;538(1-3):60-4.
The hydrolysis of lysophospholipids and nucleotides by autotaxin (NPP2) involves a single catalytic site.
Gijsbers R1, Aoki J, Arai H, Bollen M.
Author information
1
Afdeling Biochemie, Faculteit Geneeskunde, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium.
https://pubpeer.com/publications/E6911A107D4644DEB990ED46D47363
J Neurosci. 2009 Oct 14;29(41):13079-89. doi: 10.1523/JNEUROSCI.3610-09.2009.
Protein phosphatase 1 regulates the histone code for long-term memory.
Kyoko Koshibu,1
* Johannes Gra¨ff,1
* Monique Beullens,3 Fabrice D. Heitz,1 Dominik Berchtold,1,2 Holger Russig,1
Me´lissa Farinelli,1 Mathieu Bollen,3 and Isabelle M. Mansuy1
1
Brain Research Institute, Medical Faculty of the University of Zu¨rich and Department of Biology of the Swiss Federal Institute of Technology, and 2
Institute
for Human Movement Sciences and Sport, Department of Biology of the Swiss Federal Institute of Technology, CH-8057 Zurich, Switzerland, and
3
Laboratory of Biosignaling and Therapeutics, Department of Molecular Cell Biology, University of Leuven, B-3000 Leuven, Belgium.
https://pubpeer.com/publications/F7D5AFBD0F09D185017B5D7613B9DD
Figure 3.
J Biol Chem. 2007 Feb 2;282(5):3282-92. Epub 2006 Dec 1.
YPI1 and SDS22 proteins regulate the nuclear localization and function of yeast type 1 phosphatase Glc7.
Leda Pedelini‡,1, Maribel Marquina§, Joaquin Ariño§, Antonio Casamayor§, Libia Sanz‡, Mathieu Bollen¶, Pascual Sanz‡,2 and Maria Adelaida Garcia-Gimeno‡
– Author Affiliations
‡Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (CSIC), Jaime Roig 11, 46010 Valencia, Spain, the §Department Bioquimica i Biologia Molecular, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain, and the ¶Department of Molecular Cell Biology, Faculty of Medicine, Catholic University of Leuven, Herestraat 49, B-3000 Leuven, Belgium.
https://pubpeer.com/publications/355F795CF6B4FE6F072DCDCC50110F
Figure 1C.
2017 correction notice to figures 6A and 7A 2004 paper by same senior author.
http://www.biochemj.org/content/474/24/4273.long
Biochem J. 2004 Jul 1;381(Pt 1):71-7.
Substrate-specifying determinants of the nucleotide pyrophosphatases/phosphodiesterases NPP1 and NPP2.
Cimpean A1, Stefan C, Gijsbers R, Stalmans W, Bollen M.
Author information
1
Afdeling Biochemie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Herestraat 49, B-3000 Leuven, Belgium.
J Biol Chem. 2004 Mar 5;279(10):8642-7. Epub 2003 Dec 29.Inhibition of spliceosome assembly by the cell cycle-regulated protein kinase MELK and involvement of splicing factor NIPP1.Vulsteke V1, Beullens M, Boudrez A, Keppens S, Van Eynde A, Rider MH, Stalmans W, Bollen M.Author information1Afdeling Biochemie, Faculteit Geneeskunde, Catholic University of Leuven, B-3000 Leuven, Belgium.
Figure 1. Much more similar than you would expect.
See: https://imgur.com/oJIcqIj
J Biol Chem. 2005 Nov 18;280(46):38862-9. Epub 2005 Sep 14.Nucleocytoplasmic shuttling of the splicing factor SIPP1.Llorian M1, Beullens M, Lesage B, Nicolaescu E, Beke L, Landuyt W, Ortiz JM, Bollen M.Author information1Afdelingen Biochemie, Faculteit Geneeskunde, KULeuven, B-3000 Leuven, Belgium.
Figure 6C. Much more similar than you would expect.
See: https://imgur.com/A6sklIl