| An immunosurveillance mechanism controls cancer cell ploidy. | |
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MedLine Citation:
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PMID: 23019653 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cancer cells accommodate multiple genetic and epigenetic alterations that initially activate intrinsic (cell-autonomous) and extrinsic (immune-mediated) oncosuppressive mechanisms. Only once these barriers to oncogenesis have been overcome can malignant growth proceed unrestrained. Tetraploidization can contribute to oncogenesis because hyperploid cells are genomically unstable. We report that hyperploid cancer cells become immunogenic because of a constitutive endoplasmic reticulum stress response resulting in the aberrant cell surface exposure of calreticulin. Hyperploid, calreticulin-exposing cancer cells readily proliferated in immunodeficient mice and conserved their increased DNA content. In contrast, hyperploid cells injected into immunocompetent mice generated tumors only after a delay, and such tumors exhibited reduced DNA content, endoplasmic reticulum stress, and calreticulin exposure. Our results unveil an immunosurveillance system that imposes immunoselection against hyperploidy in carcinogen- and oncogene-induced cancers. |
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Authors:
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Laura Senovilla; Ilio Vitale; Isabelle Martins; Maximilien Tailler; Claire Pailleret; Mickaël Michaud; Lorenzo Galluzzi; Sandy Adjemian; Oliver Kepp; Mireia Niso-Santano; Shensi Shen; Guillermo Mariño; Alfredo Criollo; Alice Boilève; Bastien Job; Sylvain Ladoire; François Ghiringhelli; Antonella Sistigu; Takahiro Yamazaki; Santiago Rello-Varona; Clara Locher; Vichnou Poirier-Colame; Monique Talbot; Alexander Valent; Francesco Berardinelli; Antonio Antoccia; Fabiola Ciccosanti; Gian Maria Fimia; Mauro Piacentini; Antonio Fueyo; Nicole L Messina; Ming Li; Christopher J Chan; Verena Sigl; Guillaume Pourcher; Christoph Ruckenstuhl; Didac Carmona-Gutierrez; Vladimir Lazar; Josef M Penninger; Frank Madeo; Carlos López-Otín; Mark J Smyth; Laurence Zitvogel; Maria Castedo; Guido Kroemer |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Science (New York, N.Y.) Volume: 337 ISSN: 1095-9203 ISO Abbreviation: Science Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-09-28 Completed Date: 2012-10-02 Revised Date: 2012-12-19 |
Medline Journal Info:
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Nlm Unique ID: 0404511 Medline TA: Science Country: United States |
Other Details:
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Languages: eng Pagination: 1678-84 Citation Subset: IM |
Affiliation:
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INSERM, U848, Villejuif, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calreticulin / immunology Cell Line, Tumor Common Variable Immunodeficiency / genetics DNA, Neoplasm / analysis, genetics Endoplasmic Reticulum Stress / immunology* Eukaryotic Initiation Factor-2 / metabolism Humans Immunocompetence Immunologic Surveillance* Mice Mice, Inbred BALB C Neoplasms / chemically induced, genetics*, immunology* Phosphorylation Ploidies* |
| Chemical | |
Reg. No./Substance:
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0/Calreticulin; 0/DNA, Neoplasm; 0/Eukaryotic Initiation Factor-2 |
| Comments/Corrections | |
Comment In:
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Science. 2012 Sep 28;337(6102):1616-7
[PMID:
23019639
]
Nat Rev Immunol. 2012 Nov;12(11):745 [PMID: 23037554 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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