The authors revisited their experiments after another lab was unable to replicate their data, about proteins that may play a role in lung cancer.
The first author told Nature News in 2013 that the paper may have helped her secure her current position at the Novartis Institutes for Biomedical Research in Massachusetts.
Pulling “Cytohesins are cytoplasmic ErbB receptor activators” appears to be a case of doing the right thing, given the detailed retraction notice:
In Bill et al., we identified the cytohesin ARNO as an ErbB receptor activator that enhances receptor autophosphorylation in H460 and SkBr3 cells. Cell-free reconstitution with purified proteins showed that ARNO enhances EGF receptor autophosphorylation by direct interaction with the intracellular domain of the receptor (EGFR-ICD). We were recently notified by Cell that the laboratory of Dr. Oreste Segatto was unable to replicate these effects in HeLa cells or under cell-free reconstituted conditions. Although we reproducibly observe 1.6-fold ARNO-dependent stimulation of cellular EGFR autophosphorylation and partial colocalization of ARNO with EGFR in plasma membrane sheets of HeLa cells, we cannot reproduce the data showing direct stimulation of EGFR-ICD autophosphorylation by ARNO-Sec7 in a cell-free reconstitution system (shown in Figures 5D and S5D). Thus, the conclusion that ARNO enhances receptor activation by direct interaction with EGFR-ICD is no longer supported by experimental evidence. We maintain the view that cellular EGFR autophosphorylation is enhanced by ARNO, that ARNO and EGFR colocalize at the plasma membrane, and that ARNO binds to the EGFR-ICD. Nevertheless, our inability to reproduce the data in Figures 5D and S5D compromises our confidence in the proposed mechanism of this regulation. Therefore, we wish to retract the paper. We apologize for any inconvenience that may have resulted from its publication. Franziska Thorwith could not be reached about this retraction.
The paper has been cited 48 times, according to Thomson Reuters Web of Knowledge.
In 2013, Bill told Nature News some of the backstory behind the paper’s publication. According to “Science publishing: The golden club,” it may have helped her secure her current position:
Bill says that she and her adviser had initially aimed for the wider exposure that would come from publishing in Nature. But they say that they received a tough set of reviews that required more experiments. When Bill resubmitted the paper with the extra data, Nature‘s editors decided that the paper was too long and technical, she says, but Cell accepted the paper in its expanded form.
Bill says that beyond the world of biomedical science, a Nature or Science paper would have boosted her reputation more. But within her field, she says, the Cell paper had a big impact. It may have helped her to land her current position, especially because the laboratory at the German university where she did her PhD was not well known outside that country. The Cell paper showed that she could develop and test a promising novel hypothesis. “I got positive feedback everywhere I applied,” she says.
Update, May 20 2:35 PM:
Famulok pointed us to a correspondence by Segatto published in the same issue as the retraction notice which details criticisms of the paper. He told us:
The Cell Editor informed us in early April 2015 that a “Matters Arising“ article [Segatto’s correspondence] had been submitted to Cell regarding our paper and included the submission in the email.
The title of that article is “Lack of Evidence that CYTH2/ARNO Functions as a Direct Intracellular EGFR Activator.”
We submitted a response to the MA entitled: “Further evidence for the cytohesin ARNO acting as a cytoplasmic EGFR activator” in June 2015 to Cell, in which we showed that ARNO colocalizes with the EGFR in HeLa plasma membrane sheets, stimulates the autophosphorylation in HeLa cells, and in vitro binding data using methods independent of those originally used that confirmed binding between ARNO and the EGFR. The response did not contain data on the cell-free activation of EGFR autophosphorylation by ARNO because we saw variations among independent experiments. We then spent an additional 2 months on the cell-free experiments but could not reproduce the earlier results, and informed the editor about this.
I thank my coworkers and colleagues for their professionalism, reliability, and hard work during this process.
That response was not published after the authors decided to retract the paper.
He told us what he is doing next:
We are performing experiments to reconcile the results that support our notion that ARNO is a cytoplasmic EGFR activator with the failure to reproduce the cell-free autophosphorylation data.
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