CD95L cell surface cleavage triggers a prometastatic signaling pathway in triple-negative breast cancer
Authors: Florence Godey
Marine Malleter
Patrick Legembre
Loic Campion
Yves Collette
Pierre Vacher
Sébastien Tauzin
Armelle Goubard
Pascal Jézéquel
Mario Campone
Jean Levêque
Rémy Castellano
Gaëtan MacGrogan
Laure Debure
Alban Bessede
Thomas Ducret
Journal: Cancer research (2013)
Discipline: CLINICAL MEDICINE
Keywords: Triple-negative breast cancers; CD95 ligand; metastatic dissemination; metalloprotease; endothelial cells
Affiliations: Authors' Affiliations: Inserm U1085-IRSET, Equipe Labellisée Ligue Contre Le Cancer; Université de Rennes-1; Centre Eugène Marquis, rue bataille Flandres Dunkerque, Rennes; ImmuSmol, 15 Rue Amiral Prouhet, Pessac; Inserm, U1068; Institut Paoli-Calmettes; Aix-Marseille Université, CNRS, UMR 7258, Marseille; ICO-René Gauducheau, Bd J. Monod, Saint-Herblain; Université de Bordeaux; Inserm U1045, Université Bordeaux Segalen; and Inserm U916, Institut Bergonié, Bordeaux, France.

Abstract:  Triple-negative breast cancers (TNBC) lacking estrogen and progesterone receptors and HER2 amplification have a relatively high risk of metastatic dissemination, but the mechanistic basis for this risk is not understood. Here, we report that serum levels of CD95 ligand (CD95L) are higher in patients with TNBC than in other patients with breast cancer. Metalloprotease-mediated cleavage of CD95L expressed by endothelial cells surrounding tumors generates a gradient that promotes cell motility due to the formation of an unconventional CD95-containing receptosome called the motility-inducing signaling complex. The formation of this complex was instrumental for Nox3-driven reactive oxygen species generation. Mechanistic investigations revealed a Yes-Orai1-EGFR-PI3K pathway that triggered migration of TNBC cells exposed to CD95L. Our findings establish a prometastatic function for metalloprotease-cleaved CD95L in TNBCs, revisiting its role in carcinogenesis. 

Retracted: No

PubPeer comments:
 Fig. 5D: CD95 and c-yes stainings look more similar than one would expect. And CD95 staining from Fig. 5D looks very different from the one in Fig. 5C (same cell line, same treatment). Supporting Fig. 5C and H: pictures for u201ccontrolu201d and u201cuntreatedu201d look identical. But supposed to be from different cell lines (MDA-MB-231 for Fig. S5C, MDA-MB-468 for Fig.S5H). ![file] , 
 The CD95 control (lysates) for CD95 immunoprecipitations in MDA-MB-468 cells (Figure 5D) was missing and instead, two c-yes loading controls (src kinase) were depicted. We modified the figure by adding the CD95 control for this experiment (see attached figures). Boyden chamber images of the MDA-MB-231 and MDA-MB-468 TNBC cells were identical in Supporting Figures 5C and 5H. The mistake came from pictures shown for the MDA-MB-468 cell line. Therefore, we replaced these pictures by the correct images (see attached figures). These modified figures have been sent to the editor of Cancer Research for correction.![file] , 
 2020 correction. https: cancerres.aacrjournals.org content 80 3 639 In the original version of this article (1), the Western blot image used in Fig. 5D to represent CD95 lysate was inadvertently duplicated from the image of c-yes lysate. The image has been replaced with the intended image for CD95 lysate. In addition, in Supplementary Fig. S5H MDA-MB-468 cells, the cell migration images for control and cl-CD95L in the untreated group were inadvertently duplicated from the control group of Supplementary Fig. S5C MDA-MB-231 cells. The images have been replaced with the intended images for MDA-MB-468 cells. These corrections are reflected in the latest online HTML and PDF versions of the article. The authors regret these errors. Reference 1.u21b5Malleter M, Tauzin S, Bessede A, Castellano R, Goubard A, Godey F, et al. CD95L cell surface cleavage triggers a prometastatic signaling pathway in triple-negative breast cancer. Cancer Res 2013;73:6711u201321. ,