A cellular machine generating apoptosis-prone aneuploid cells

Selective Resistance of Tetraploid Cancer Cells against DNA Damage‐Induced Apoptosis

“…Chromosomal loss from the tetraploid genome and/or asymmetric cell division may generate an aneuploid offspring. We have obtained evidence that aneuploid daughter cells produced by the division of polyploid mother cells die from apoptosis shortly after their generation 5,43,44 . At present, we ignore the question of whether the death of such aneuploid cells is a result of pro‐apoptotic signals received during the asymmetric division signals or whether it results from acutely lethal metabolic deficiencies, for example, on account of a nullisomy of autosomes or gene dosage disequilibria.…”

“…Polyploidization may result from two distinct processes, namely cell fusion 3,4 or by duplication of the normal chromosomal number in the absence of nuclear and cellular division. Fusion between cells from the same type (homotypic fusion) can be induced in vitro and can lead to the generation of pseudodiploid, aneuploid cells generated by an asymmetric reduction‐mitosis 5 . Fusion between distinct cell types (heterotopic fusion) has been documented in vivo , for instance between tumor cells and infiltrating cells from myeloid origin 6 and may contribute to the plasticity of cancer.…”

“…Fusion between cells from the same type (homotypic fusion) can be induced in vitro and can lead to the generation of pseudodiploid, aneuploid cells generated by an asymmetric reduction-mitosis. 5 Fusion between distinct cell types (heterotopic fusion) has been documented in vivo, for instance between tumor cells and infiltrating cells from myeloid origin 6 and may contribute to the plasticity of cancer. Duplication of chromosomes within the same cell occur physiologically through endoreplication (DNA replication without mitosis) or endomitosis (karyokinesis without cytokinesis) or, pathologically, through mitotic failure.…”

A novel source of tetraploid cancer cell precursors: telomere insufficiency links aging to oncogenesis

“…Accordingly, the loss of p53 function is associated with tetraploidy in Barett's esophagus (Finley et al, 2006) and in early cervical cancers (Skyldberg et al, 1999). Tetraploidy constitutes a metastable state because tetraploid cells tend to lose chromosomes progressively during aberrant dipolar mitoses (Ganem and Pellman, 2007) and/or undergo multipolar mitosis during which chromosomes are distributed among the daughter cells in a near-to-random manner (Roumier et al, 2005;Vitale et al, 2010). This latter process is facilitated through the activation of the oncogene mos, which inhibits the aggregation of supernumerary centrosomes and facilitates multipolar divisions leading to the generation of three or more daughter cells per mitosis (Vitale et al, 2010).…”

Involvement of p38α in the mitotic progression ofp53-/-tetraploid cells

“…Key words: aneuploidy, apoptosis, centrosome, colon carcinoma, MOS further cell divisions because nullisomies (the total absence of one particular chromosome) and polysomies (the presence of one or more extra chromosomes) are always and most often lethal, respectively. [20][21][22] Still, in exceptional cases, daughter cells arising from multipolar divisions survive and yield an aneuploid progeny. Indeed, when p53 -/-tetraploid clones are cultured for a prolonged period, they tend to accumulate an ever-increasing subpopulation of pseudo-diploid cells, which have been formed through multipolar divisions.…”