Immunological control of cell cycle aberrations for the avoidance of oncogenesis: the case of tetraploidy

Tetraploid cells—cells that contain twice the normal amount of DNA—are more prone to neoplastic transformation than their normal, diploid counterparts since they are genomically unstable and frequently undergo asymmetric, multipolar cell divisions. Similar to many other genomic aberrations, tetraplo...

Full description

Saved in:
Bibliographic Details
Published in:Annals of the New York Academy of Sciences 2013-05, Vol.1284 (1), p.57-61
Main Authors: Senovilla, Laura, Galluzzi, Lorenzo, Castedo, Maria, Kroemer, Guido
Format: Article
Language:English
Subjects:
Animals
calreticulin
Calreticulin - metabolism
Cell Cycle
Cell Transformation, Neoplastic - genetics
Chromosome Aberrations
CT26 cells
DNA - analysis
eIF2α phosphorylation
Endoplasmic Reticulum - metabolism
Eukaryotic Initiation Factor-2 - metabolism
HMGB1
HMGB1 Protein - metabolism
Humans
Immune system
Ligands
Neoplasms - pathology
Neoplasms - prevention & control
nocodazole
Nocodazole - pharmacology
p53
Proteins
Tetraploidy
Tumor Suppressor Protein p53 - metabolism
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Tetraploid cells—cells that contain twice the normal amount of DNA—are more prone to neoplastic transformation than their normal, diploid counterparts since they are genomically unstable and frequently undergo asymmetric, multipolar cell divisions. Similar to many other genomic aberrations, tetraploidization is normally avoided by multiple, nonredundant cell‐intrinsic mechanisms that are tied to cell cycle checkpoints. Unexpectedly, tetraploidization is also under the control of a cell‐extrinsic mechanism determined by the immune system. Indeed, oncogene‐ or carcinogen‐induced cancers developing in immunodeficient mice contain cells with a higher DNA content than similar tumors growing in immunocompetent hosts. Moreover, cancer cell lines that have been rendered tetraploid in vitro grow normally in immunodeficient mice, yet almost fail to generate tumors in immunocompetent animals. One of the mechanisms whereby the immune system recognizes tetraploid cells originates from tetraploidy causing an endoplasmic reticulum (ER) stress response that culminates in the exposure of the ER protein calreticulin on the cell surface. Hence, tetraploidy exemplifies a potentially oncogenic alteration that is repressed by a combination of cell‐autonomous mechanisms and immunosurveillance. Oncogenesis and tumor progression require the simultaneous failure of both such control systems.
ISSN:0077-8923
1749-6632
DOI:10.1111/nyas.12072