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Following five years of criticism, a group of researchers based at Stanford and elsewhere have retracted a 2006 paper in Nature for “image anomalies.”

The notice for “Lysyl oxidase is essential for hypoxia-induced metastasis” reads:

We, the authors, are retracting this Article owing to issues that have come to our attention regarding figure assembly and data availability. Image analysis of the data has showed several image anomalies in Fig. 4c, Supplementary Figs. 1a, e and 4a. Nature has informed us that the quality and integrity of these images are not in line with journal policies. In particular, the panels affected include Supplementary Fig. 4a, which demonstrates that the shRNA construct used in the manuscript induces a reduction of LOX protein. No original data are available for the affected panels or other data included in the manuscript. We believe that the key findings of the paper are still valid as replicated by others. However, given the issues described above and the absence of original data, we have concluded that the most appropriate course of action is to retract the Article. All authors agree with the Retraction.

Comments about the paper first appeared on PubPeer in 2015. Over the ensuing years first author Janine Erler’s ex-husband Rune Linding, also a scientist, and a colleague of Linding’s commissioned independent analyses of the images in the papers. Those analyses found potential duplications and splicing, as we reported in 2018.

The paper has been cited 960 times, according to Clarivate Analytics’ Web of Science, and 62 of those citing papers were designated “highly cited papers.” Of the 960 citations, 134 appeared since March 2018.

Asked to comment on the retraction, first author Erler, now of the University of Copenhagen, sent us the following comment, writing that “You may use the following quote in full – I do not agree to partial use.”

As stated in the retraction text, Nature informed us that some of the images in the paper were not in line with their policies. Due to the age of the paper, we lacked the original data and therefore felt the appropriate action was to retract the paper. The paper is highly cited (961 citations) and the findings highly reproduced by other researchers. We therefore stand by the scientific findings. Importantly, this paper had nothing to do with the development, testing or clinical trials of the LOXL2 targeting antibody Simtuzumab.

The paper was one of more than 400 references cited in a patent application to develop inhibitors of enzyme lysyl oxidase (LOX) enzymes to prevent and treat cancer metastases. Gilead abandoned that approach in 2016 after failed trials. But Steven D. Nathan, director of the Advanced Lung Disease Program and director of the Lung Transplant Program at Inova Fairfax Hospital, told us in 2018 that he “highly doubt[ed] the company developed this based on one study. I think it probably would have been developed anyway.”

In 2018, Nature told us that it was “following an established process to investigate the issues” but could not comment on the ongoing investigation. We asked Nature why it was taking action now. A spokesperson told us:

In general, whenever concerns are raised about papers we have published, whether by the original authors or by other researchers and readers, we look into them carefully, following an established process, consulting the authors and, where appropriate, seeking advice from peer reviewers and other external experts. Once this process has concluded and we have the necessary information to make an informed decision, we will follow up with the response that is most appropriate in order to maintain the accuracy of the scientific record. These issues are often complex, however, and as a result, it can take time for editors and authors to fully unravel them.

In addition to the retraction, Erler has had two papers corrected and one subject to an expression of concern. The EOC, in Cancer Research, reads:

The editors were made aware of concerns regarding this article (1). An internal review by the editors determined that lanes 2–4 of the pSMAD2 Western blot image in Supplementary Fig. S3C are identical to the LOX Western blot image in Supplementary Fig. S3D.

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