In vitro effects of a small-molecule antagonist of the Tcf/ß-catenin complex on endometrial and endometriotic cells of patients with endometriosis
Authors: Claude Darcha
Sachiko Matsuzaki
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Wnt/ß-catenin signaling; endometriosis; cell proliferation; migration; invasion
Affiliations: CHU Clermont-Ferrand, CHU Estaing, Chirurgie Gynécologique, 1, Clermont-Ferrand, France. 

Abstract:  Background: Our previous studies suggested that aberrant activation of Wnt/ß-catenin signaling might be involved in the pathophysiology of endometriosis. We hypothesized that inhibition of Wnt/ß-catenin signaling might result in inhibition of cell proliferation, migration, and/or invasion of endometrial and endometriotic epithelial and stromal cells of patients with endometriosis. Objectives: The aim of the present study was to evaluate the effects of a small-molecule antagonist of the Tcf/ß-catenin complex (PKF 115-584) on cell proliferation, migration, and invasion of endometrial and endometriotic epithelial and stromal cells. Methods: One hundred twenty-six patients (78 with and 48 without endometriosis) with normal menstrual cycles were recruited. In vitro effects of PKF 115-584 on cell proliferation, migration, and invasion and on the Tcf/ß-catenin target genes were evaluated in endometrial epithelial and stromal cells of patients with and without endometriosis, and in endometrial and endometriotic epithelial and stromal cells of the same patients. Results: The inhibitory effects of PKF 115-584 on cell migration and invasion in endometrial epithelial and stromal cells of patients with endometriosis prepared from the menstrual phase were significantly higher than those of patients without endometriosis. Levels of total and active forms of MMP-9 were significantly higher in epithelial and stromal cells prepared from menstrual endometrium in patients with endometriosis compared to patients without endometriosis. Treatment with PKF 115-584 inhibited MMP-9 activity to undetectable levels in both menstrual endometrial epithelial and stromal cells of patients with endometriosis. The number of invasive cells was significantly higher in epithelial and stromal cells of endometriotic tissue compared with matched eutopic endometrium of the same patients. Treatment with PKF 115-584 decreased the number of invasive endometriotic epithelial cells by 73% and stromal cells by 75%. Conclusions: The present findings demonstrated that cellular mechanisms known to be involved in endometriotic lesion development are inhibited by targeting the Wnt/β-catenin pathway. 

Retracted: No

PubPeer comments:
 I found some concerning duplication in some experiments performed by authors in this article. I will list below some examples: Extended Figure 1: i) Mean and SEM are the exactly same values for CCNA2 ![file] ii) Duplicated values in Population doublings assay ![file] iii) SEM and Mean values are duplicated for CCNE2 ![file] Figure 8: Several duplications of values can be found in qPCR assays ![file] ![file] Could authors check these concerns please? , 
 Considering a non-overlapping set of regions were selected for this analysis could the authors check why the boxplots are almost identical. Some of the boxes seem identical with just the mean shifted. ![file] , 
 Correction to: Nature Cell Biology https: doi.org 10.1038 s41556-020-0529-5, published online 8 June 2020 https: www.nature.com articles s41556-020-00589-3  In the version of this Article originally published, there were several errors in Fig. 8, Extended Data Fig. 1, and source data. Mean values for CCNA2 were inadvertently copied as s.e.m. values for CCNA2 in statistical source data for Extended Data Fig. 1m. In addition, the s.e.m. values for CCNE2 were inadvertently copied as mean values for CDKN2A in statistical source data for Extended Data Fig. 1q. Corresponding Extended Data Fig. 1q was corrected accordingly to reflect the expression values of CDKN2A. Furthermore, the original statistical source data for Fig. 8c,d,f contained identical raw values and invalid integers. In addition, Irak3 expression was not displayed in the original heatmap of Fig. 8f, and the rows for CXCL5 and TGFB2 were swapped in the statistical source data file for Fig. 8d. The corrections lead to several, minor changes in the fold-change mean values that result in minimal alterations in the heatmap visualization in Fig. 8c,d,f. Additional methodology details on qPCR have also been added to the section of u201cQuantitative RT-qPCRu201d in Methods. The errors have been corrected. ,