The apoptotic members CD95, BclxL, and Bcl-2 cooperate to promote cell migration by inducing Ca(2+) flux from the endoplasmic reticulum to mitochondria
Authors: A Fouqu√©
P Legembre
P Vacher
M Malleter
E Lepvrier
M Ovize
C Li
Y Gouriou
V Delcroix
T Ducret
M Hammadi
L Debure
Journal: Cell death and differentiation (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Metalloprotease-processed CD95L; PI3K/Ca(2+) signaling pathway; triple-negative breast cancer (TNBC) cells; cl-CD95L; poor prognosis
Affiliations: Inserm ER440-Oncogenesis, Stress and Signaling, Equipe Labellis√©e Ligue Contre Le Cancer, Rue Bataille Flandres Dunkerque, Rennes 35042, France., Centre Eug√®ne Marquis, Inserm ERL440-OSS, Rue Bataille Flandres Dunkerque, Rennes 35042, France., Universit√© de Rennes-1, 2 Avenue du Prof. L√©on Bernard, Rennes 35043, France., Laboratoire Commun, OncoTrial UMS Biosit/Biotrial 7-9 Rue Jean-Louis Bertrand, Rennes 35000, France., Inserm U1060, CarMeN, Universit√© Claude Bernard Lyon 1, 8 Avenue Rockfeller, Lyon 69373, France., Universit√© de Bordeaux, 146 Rue L√©o Saignat, Bordeaux 33076, France., Inserm U1218, Institut Bergoni√©, 229 Cours de l'Argonne, Bordeaux 33076, France., Hospices Civils de Lyon, H√¥pital Louis Pradel, Services D'explorations Fonctionnelles Cardiovasculaires et CIC de Lyon, Lyon 69394, France., Inserm U1045, Centre de Recherche Cardiothoracique de Bordeaux, 146 Rue L√©o Saignat, Bordeaux 33076, France., Molecular Targets Group, James Graham Brown Cancer Center, Departments of Medicine, and Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA.

Abstract:  Metalloprotease-processed CD95L (cl-CD95L) is a soluble cytokine that implements a PI3K/Ca(2+) signaling pathway in triple-negative breast cancer (TNBC) cells. Accordingly, high levels of cl-CD95L in TNBC women correlate with poor prognosis, and administration of this ligand in an orthotopic xenograft mouse model accelerates the metastatic dissemination of TNBC cells. The molecular mechanism underlying CD95-mediated cell migration remains unknown. Here, we present genetic and pharmacologic evidence that the anti-apoptotic molecules BclxL and Bcl-2 and the pro-apoptotic factors BAD and BID cooperate to promote migration of TNBC cells stimulated with cl-CD95L. BclxL was distributed in both endoplasmic reticulum (ER) and mitochondrion membranes. The mitochondrion-localized isoform promoted cell migration by interacting with voltage-dependent anion channel 1 to orchestrate Ca(2+) transfer from the ER to mitochondria in a BH3-dependent manner. Mitochondrial Ca(2+) uniporter contributed to this flux, which favored ATP production and cell migration. In conclusion, this study reveals a novel molecular mechanism controlled by BclxL to promote cancer cell migration and supports the use of BH3 mimetics as therapeutic options not only to kill tumor cells but also to prevent metastatic dissemination in TNBCs. 

Retracted: No

PubPeer comments:
 Figure 1G Control for sh BCL2#06 and 61 look identical  , 
 Also two images very similar (identical ?) in Figures 4C and 6B for BclxL-MT+cl-CD95L condition. The OD range for BclxL-MT+Cl-CD95L is very different between those figures. So all the conditions displayed in Figure 4C and 6B were probably not tested in the same experimental set (... and so these images should probably not be identical).  , 
 Boyden chamber pictures were not checked enough and Images 1G and 6B have to be modified. Accordingly, I contacted the editor of CDD to replace these images by those attached , 
 #3 Was this article corrected? I did not easily locate the correction at the journal site. ,