A link between mitotic defects and mitotic catastrophe: detection and cell fate

Abstract

Although the phenomenon of mitotic catastrophe was first described more than 80 years ago, only recently has this term been used to explain a mechanism of cell death linked to delayed mitosis. Several mechanisms have been suggested for mitotic catastrophe development and cell fate. Depending on molecular perturbations, mitotic catastrophe can end in three types of cell death, namely apoptosis, necrosis, or autophagy. Moreover, mitotic catastrophe can be associated with different types of cell aging, the development of which negatively affects tumor elimination and, consequently, reduces the therapeutic effect. The effective triggering of mitotic catastrophe in clinical practice requires induction of DNA damage as well as inhibition of the molecular pathways that regulate cell cycle arrest and DNA repair. Here we discuss various methods to detect mitotic catastrophe, the mechanisms of its development, and the attempts to use this phenomenon in cancer treatment.

Cell Type-Specific Patterns in the Accumulation of DNA Damage Following Multifractional Radiation Exposure

“…Following a severe genotoxic event, these cells enter an endoreplication cycle where mitosis is entirely circumvented as a means to evade apoptosis. Polyploid cells are more likely to undergo mitotic catastrophe, which leads to increased micronuclei formation [ 46 ]. The inactivation of p53 in these cells bypasses G1 cell cycle checkpoints mediated by p53 target genes such as p21WAF1/CIP1, leading to accumulation at G2, checkpoint adaptation and aberrant mitosis yielding micronuclei [ 30 , 47 ].…”

No Time to Die: How Kidney Cancer Evades Cell Death

“…Those treatments, independently from the sequence chosen, inevitably fail in most cases. Therefore, understanding on the molecular basis of the disease [ 179 , 180 , 181 , 182 ], and the way in which cell death could be triggered [ 183 , 184 , 185 ] in RCCs, is still a valuable field of research. Programmed cell death modalities, which form apoptosis to necroptosis, are normally kept inactive in the development of RCCs, to favor cancer cell growth.…”

Radiotherapy modulates tumor cell fate decisions: a review

“…Mitotic catastrophe usually occurs during or after abnormal mitosis. Due to abnormal cell mitosis, cells undergo atypical chromosome segregation and cell division, resulting in giant cells with abnormal nuclear morphology, multiple nuclei, and multiple micronuclei [ 109 ]. The mechanism of mitotic catastrophe is related to the promotion of mitosis and centrosome hyperamplification [ 110 ].…”