@article{43ad4e4768244446af05a067daac2cfc,
title = "Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246",
abstract = "TP53 mutants (mutp53) are involved in the pathogenesis of most human cancers. Specific mutp53 proteins gain oncogenic functions (GOFs) distinct from the tumor suppressor activity of the wild-type protein. Tumor-associated macrophages (TAMs), a hallmark of solid tumors, are typically correlated with poor prognosis. Here, we report a non-cell-autonomous mechanism, whereby human mutp53 cancer cells reprogram macrophages to a tumor supportive and anti-inflammatory state. The colon cancer cells harboring GOF mutp53 selectively shed miR-1246-enriched exosomes. Uptake of these exosomes by neighboring macrophages triggers their miR-1246-dependent reprogramming into a cancer-promoting state. Mutp53-reprogammed TAMs favor anti-inflammatory immunosuppression with increased activity of TGF-β. These findings, associated with poor survival in colon cancer patients, strongly support a microenvironmental GOF role for mutp53 in actively engaging the immune system to promote cancer progression and metastasis.",
author = "Tomer Cooks and Pateras, {Ioannis S.} and Jenkins, {Lisa M.} and Patel, {Keval M.} and Robles, {Ana I.} and James Morris and Tim Forshew and Ettore Appella and Gorgoulis, {Vassilis G.} and Harris, {Curtis C.}",
note = "Funding Information: 1Laboratory of Human Carcinogenesis, NCI-CCR, National Institutes of Health, Bethesda 20892-4258 MD, USA. 2Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National Kapodistrian University of Athens, 75 Mikras Asias St, Athens GR-11527, Greece. 3Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda 20892-4258 MD, USA. 4Addenbrooke{\textquoteright}s Hospital, Hills Road, Cambridge CB2 0QQ, UK. 5Cancer Research UK, Cambridge Research Institute, Robinsons Way, Cambridge CB2 0RE, UK. 6UCL Cancer Institute, Huntley St, Camden Town, London WC1E 6DD, UK. 7Biomedical Research Foundation of the Academy of Athens, 4 Soranou Ephessiou St., GR-11527 Athens, Greece. 8Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health, Science Centre, Wilmslow Road, Manchester M20 4QL, UK. Correspondence and requests for materials should be addressed to C.C.H. (email: curtis_harris@nih.gov) Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-018-03224-w",
language = "English",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}
