2014 ORI finding results in retraction of cancer paper with manipulated images

A paper flagged in an Office of Research Integrity notice more than one year ago has finally been retracted. According to the notice, the paper includes images manipulated by author H. Rosie Xing, a former University of Chicago cancer researcher.

The main conclusions of the paper are affected by the ORI finding, according to the retraction note from Molecular Cancer Therapeutics. But otherwise, the note contains information that was available in the ORI finding, published in December 2014.

“Pharmacologic Inactivation of Kinase Suppressor of Ras1 Sensitizes Epidermal Growth Factor Receptor and Oncogenic Ras-Dependent Tumors to Ionizing Radiation Treatment” has been cited seven times, according to Thomson Scientific’s Web of Knowledge — twice since the ORI finding came out.

The retraction note explains which images were affected by the manipulation:

The finding of misconduct impacts the main conclusions of this article, specifically, that images used in the article “had been among a set of manipulated images produced while at another institution, which had been found to be false by that institution. ORI found that respondent falsely reported these images in Figs. 1D, 2A, and Supplementary Fig. S1B and S1C” (2).

The note outlines the falsifications as they were reported in the 2014 ORI notice:

1. Falsely labeled immunoblots in Figs. 1D and 2A as follows:

   1. Figure 1D (bottom panel), representing the total ERK levels in extracts from cells exposed to 15 Gy of gamma radiation for 0–120 minutes, by using results from an unrelated experiment for MAPK levels in extracts from cells exposed to 2, 12, or 20 Gy of gamma irradiation for 1, 5, 20, or 60 minutes

   2. Figure 2A (KSR1 panel), representing a control Flag-KSR1 immunoblot for extracts of cells transfected with control (TRE), wild-type KSR (KSR-S), or dominant negative inactive KSR (DN-KSR) exposed to no radiation or gamma irradiation for 5 minutes, by using results form an unrelated experiment for KSR-transfected cells (KSR-S) irradiated with 0, 2, 5, 20, 15, 20 Gy irradiation

   3. Figure 2A (ERK panel), representing a control ERK immunoblot for extracts of cells transfected with control (TRE), wild-type KSR (KSR-S), or dominant negative inactive KSR (DN-KSR) exposed to no radiation or gamma irradiation for 5 minutes, by using results from an unrelated experiment for KSR-transfected cells (KSR-S) irradiated with 0, 2, 5, 10, 15, 20 Gy irradiation

2. Falsified images in Figs. 1D, 2A, and Supplementary Fig. S1B and S1C by duplicating bands within the figures as follows:

   1. Figure 1D (top panel) for an immunoblot for p-ERK in A431 cells, by using the same bands to represent cells treated with ionizing radiation for 5 and 10 minutes with the bands for 60 and 90 minutes

   2. Figure 2A (top) for an in vitro kinase assay for p-GST-Elk-1, by duplicating lanes 2 and 5 to represent the control plasmid (TRE) at 5 minutes postradiation (lane 2) and the dominant negative inactive KSR (DN-KSR) NT lane (lane 5)

   3. Supplementary Figure S1B (middle panel) for an in vitro kinase assay for p-GST-MEK, by using the same bands to represent cells exposed to 5 and 20 Gy ionizing radiation

   4. Supplementary Figure S1C (top panel) for an immunoblot for p-MEK1/2, by using the same bands to represent cells exposed to 2 and 20 Gy ionizing radiation

This is the third retraction for Xing, who had two retractions in the Journal of Biological Chemistry before the ORI published its findings.

We’ve also unearthed a correction from 2011 for a Nature Medicine paper on which Xing is the first author, “Pharmacologic inactivation of kinase suppressor of ras-1 abrogates Ras-mediated pancreatic cancer:”

In the version of this article initially published, there are irregularities with the tubulin loading controls in lanes 1 through 4 and with the KSR1 bands in lanes 7 and 8 of Figure 2f. The authors have repeated the experiment and have provided a new figure panel that is now published as part of the correction notices linked to the HTML version and attached to the PDF version of the article. The original figures remain in both online versions of the article. The authors have also made a correction to Supplementary Figure 6b, which has been added to the supplementary file online. H. Rosie Xing does not agree to this correction.

The Nature Medicine paper has been cited 35 times.

We’ve reached out to Molecular Cancer Therapeutics to ask why it took them so long to retract the paper; we could not find contact information for Xing.

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