@article{f7388992890f48dc87f861638e4cc95a,
title = "CD47 is a direct target of SNAI1 and ZEB1 and its blockade activates the phagocytosis of breast cancer cells undergoing EMT",
abstract = "We report that CD47 was upregulated in different EMT-activated human breast cancer cells versus epithelial MCF7 cells. Overexpression of SNAI1 or ZEB1 in epithelial MCF7 cells activated EMT and upregulated CD47 while siRNA-mediated targeting of SNAI1 or ZEB1 in mesenchymal MDA-MB-231 cells reversed EMT and strongly decreased CD47. Mechanistically, SNAI1 and ZEB1 upregulated CD47 by binding directly to E-boxes in the human CD47 promoter. TCGA and METABRIC data sets from breast cancer patients revealed that CD47 correlated with SNAI1 and Vimentin. At functional level, different EMT-activated breast cancer cells were less efficiently phagocytosed by macrophages vs. MCF7 cells. The phagocytosis of EMT-activated cells was rescued by using CD47 blocking antibody or by genetic targeting of SNAI1, ZEB1 or CD47. These results provide a rationale for an innovative preclinical combination immunotherapy based on PD-1/PD-L1 and CD47 blockade along with EMT inhibitors in patients with highly aggressive, mesenchymal, and metastatic breast cancer.",
keywords = "Breast cancer, CD47, Dendritic cells, Epithelial to Mesenchymal Transition, Immune checkpoint, Macrophage, Phagocytosis and Immunotherapy, ZEB1",
author = "Noman, {Muhammad Zaeem} and {Van Moer}, Kris and Vanessa Marani and Gemmill, {Robert M.} and Tranchevent, {L{\'e}on Charles} and Francisco Azuaje and Arnaud Muller and Salem Chouaib and Thiery, {Jean Paul} and Guy Berchem and Bassam Janji",
note = "Funding Information: This work was supported by grants from: FNRS-Televie (20150327), Jans-sen Pharmaceutical, Fondation Cancer (20160517), Celgene and LIH (2013 11 05). RMG was supported by grants from the Dept. of Defense, DOD LC150622 and from the Veterans Administration, BX003333. We thank Cristina Maximo and Joshua Brown-Clay (LIH, Luxembourg) for their help in editing the manuscript. Funding Information: This work was supported by grants from: FNRS-Televie (20150327), Janssen Pharmaceutical, Fondation Cancer (20160517), Celgene and LIH (2013 11 05). RMG was supported by grants from the Dept. of Defense, DOD LC150622 and from the Veterans Administration, BX003333. We thank Cristina Maximo and Joshua Brown-Clay (LIH, Luxembourg) for their help in editing the manuscript. Publisher Copyright: {\textcopyright} 2018 Taylor & Francis Group, LLC.",
year = "2018",
month = apr,
day = "3",
doi = "10.1080/2162402X.2017.1345415",
language = "English",
volume = "7",
journal = "OncoImmunology",
issn = "2162-4011",
publisher = "Landes Bioscience",
number = "4",
}