Journal article
An immunosurveillance mechanism controls cancer cell ploidy
L Senovilla, I Vitale, I Martins, M Tailler, C Pailleret, M Michaud, L Galluzzi, S Adjemian, O Kepp, M Niso-Santano, S Shen, G Mariño, A Criollo, A Boilève, B Job, S Ladoire, F Ghiringhelli, A Sistigu, T Yamazaki, S Rello-Varona Show all
Science | Published : 2012
Abstract
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 conte..
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Awarded by Fonds Zur Forderung der Wissenschaftlichen Forschung (FWF)
Awarded by Austrian Science Fund (FWF)
Funding Acknowledgements
We are grateful to M. L. Albert (Institut Pasteur, Paris) for Ifnar1<SUP>-/-</SUP> and Ifng<SUP>-/-</SUP> mice, M. Colonna (Washington University School of Medicine, St. Louis, MO) for Cd226<SUP>-/-</SUP> mice (Dnam-1<SUP>-/-</SUP> mice), S. B. Horwitz (Albert Einstein College of Medicine, New York) for epothilone B-resistant A549 cells, R. Prywes (Columbia University, New York) for the GFP-ATF6-encoding plasmid, J. Yuan (Massachusetts Institute of Technology, Boston) for the XBP1-DBD-Venus-encoding construct, T. Reid (NIH, Bethesda, MD) for DLD-1 and DLD1+7 cell lines, and D. Metivier for assistance with fluorescence-activated cell sorting (FACS) experiments. G. K. is supported by the 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, and the LabEx Immuno-Oncology. F. M. is grateful to the Fonds Zur Forderung der Wissenschaftlichen Forschung (FWF, grants LIPOTOX, P23490-B12, P24381-B20, and W 1226-B18). L. S. and M. M. are supported by FRM. I. V., I. M., M. T., and S. A. are supported by LNC. M. N.-S. is supported by a postdoctoral contract of Junta de Extremadura (Spain) and G. M. by European Molecular Biology Organization. M. J. S. was supported by National Health and Medical Research Council (NH and MRC) Australia and the Victorian Cancer Agency. C. J. C. was supported by Leukemia Foundation of Australia, Monash University. N. M. was supported by Cancer Research Institute. J. M. P. and V. S. are supported by the Austrian Academy of Sciences, an Advanced European Research Council grant, and the European Union INFLA-CARE network. L. S., I. V., I. M., M. T., C. P., M. M., S. A., O.K., M. N.-S., S. S., G. M., A. C., A. B., B.J., S. L., F. G., A. S., T.Y., S.R.-V., C. L., V.P.-C., M. T., A. V., F. B., A. A., F. C., G. M. F., M. P., A. F., N.L.M., M. L., C.J.C., V. S., G. P., V. L., J.M.P., C.L.-O., M.J.S., and M. C. performed experiments. L. S., C. R., D. C.-G., F. M., L.Z., M. C., and G. K. designed the study. L. S., L.Z., M. C., and G. K. analyzed results. L. S., L. G., and G. K. assembled the figures and wrote the paper. The authors declare no conflicts of interest.