Heterogeneity of Cell Death

Abstract

Cell death constitutes a number of heterogeneous processes. Despite the dynamic nature of cell death, studies of cell death have primarily focused on apoptosis, and cell death has often been viewed as static events occurring in linear pathways. In this article we review cell death heterogeneity with specific focus on 4 aspects of cell death: the type of cell death; how it is induced; its mechanism(s); the results of cell death, and the implications of cell death heterogeneity for both basic and clinical research. This specifically reveals that cell death occurs in multiple overlapping forms that simultaneously occur within a population. Network and pathway heterogeneity in cell death is also discussed. Failure to integrate cell death heterogeneity within analyses can lead to inaccurate predictions of the amount of cell death that takes place in a tumor. Similarly, many molecular methods employed in cell death studies homogenize a population removing heterogeneity between individual cells and can be deceiving. Finally, and most importantly, cell death heterogeneity is linked to the formation of new genome systems through induction of aneuploidy and genome chaos (rapid genome reorganization).

Evolutionary mechanism unifies the hallmarks of cancer

“…As previously demonstrated, high doses of chemotherapeutics intended for high rates of tumor cell death that are commonly prescribed to patients can trigger chaotic genome formation and rapid changes of genome systems, which may lead to rapid emergence of an aggressive, drug-resistant tumor subpopulation. [24][25][26]57,73 Thus, the genome theory calls into question the current standard protocols of chemotherapy, as drug intervention could paradoxically promote cancer evolution when applied in the wrong phase. 75,76 Therapeutic strategies should include the aim to reduce system stress to avoid triggering fast cancer evolution.…”

“…cell death, cell proliferation, no effect, adverse effect) among cells during treatment regimens as a result of targeting specific hallmark characteristics. 56,57 Therefore, due to evolutionary dynamics, tracing a key feature is challenging as specific features may come and go during evolution, and the initial key factors might or might not play a role in the future. Perhaps the approach of dissecting the system into the simplest terms does not work well in highly dynamic situations such as cancer evolution where genome heterogeneity rules.…”

Expression of cell cycle and apoptosis regulators in thymus and thymic epithelial tumors

“…Cell cycle and death (apoptotic and non-apoptotic) regulators play crucial roles in normal tissue physiology as well as in pathological processes such as oncogenesis and inflammation [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Cell cycle regulation is achieved through a family of serine/threonine kinase holoenzyme complexes consisting of regulatory cyclin that bind to and activate catalytic cyclin-dependent kinases (CDKs) [1].…”

“…Necrosis is characterized morphologically by loss of plasma membrane integrity, swelling of organelles (e.g., endoplasmic reticulum, mitochondria) and largely intact distended nucleus, whereas apoptosis is characterized morphologically by condensation of chromatin and nuclear fragmentation [5,6,11,15,16]. Necrosis frequently occurs when cells are challenged with overwhelming stress including drug toxicity, mechanical damage, heat and pathogen infection [5,6,15].…”

Analysis of the role of RNS2 and autophagy in the turnover of ribosomal RNA in Arabidopsis thaliana

“…Early work in cell death studied each mode of cell death in isolation from other cell death mechanisms. However, accumulating evidence suggests that there is considerable overlap and signaling crosstalk between the different cell death pathways and how they are regulated (Nikoletopoulou et al 2013;Stevens et al 2013). …”