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 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.

Autore Pugliese

• Fimia Gian Maria

Tutti gli autori

• Senovilla L. , Vitale I. , Martins I. , Tailler M. , Pailleret C. , Michaud M. , Galluzzi L. , Adjemian S. , Kepp O. , Niso-Santano M. , Shen S. , Mariño G. , Criollo A. , Boilève A. , Job B. , Ladoire S. , Ghiringhelli F. , Sistigu A. , Yamazaki T. , Rello-Varona S. , Locher C. , Poirier-Colame V. , Talbot M. , Valent A. , Berardinelli F. , Antoccia A. , Ciccosanti F. , Fimia G.M. , Piacentini M. , Fueyo A. , Messina N.L. , Li M. , Chan C.J. , Sigl V. , Pourcher G. , Ruckenstuhl C. , Carmona-Gutierrez D. , Lazar V. , Penninger J.M. , Madeo F. , López-Otín C. , Smyth M.J. , Zitvogel L. , Castedo M. , Kroemer G.

Titolo volume/Rivista

SCIENCE

Anno di pubblicazione

2012

ISSN

1095-9203

ISBN

Non Disponibile

Numero di citazioni Wos

165

Ultimo Aggiornamento Citazioni

25/04/2018

Numero di citazioni Scopus

174

Ultimo Aggiornamento Citazioni

26/04/2018

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile