Journal
SCIENCE
Volume 337, Issue 6102, Pages 1678-1684Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1224922
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Funding
- Ligue Nationale contre le Cancer (LNC, Equipe labelisee)
- Agence Nationale pour la Recherche (ANR)
- European Commission (Active p53, Apo-Sys, ChemoRes, ApopTrain)
- Fondation pour la Recherche Medicale (FRM)
- Institut National du Cancer (INCa)
- Canceropole Ile-de-France
- Fondation Bettencourt-Schueller
- LabEx Immuno-Oncology
- Fonds Zur Forderung der Wissenschaftlichen Forschung (FWF) [LIPOTOX, P23490-B12, P24381-B20, W 1226-B18]
- FRM
- LNC
- Junta de Extremadura (Spain)
- European Molecular Biology Organization
- National Health and Medical Research Council (NH and MRC) Australia
- Leukemia Foundation of Australia, Monash University
- Cancer Research Institute
- Austrian Academy of Sciences
- Advanced European Research Council
- European Union INFLA-CARE network
- Austrian Science Fund (FWF) [P 23490] Funding Source: researchfish
- Austrian Science Fund (FWF) [P23490] Funding Source: Austrian Science Fund (FWF)
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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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