Abstract
BackgroundApoptosis, the most well-known type of programmed cell death, can induce in a paracrine manner a proliferative response in neighboring surviving cells called apoptosis-induced proliferation (AiP). While having obvious benefits when triggered in developmental processes, AiP is a serious obstacle in cancer therapy, where apoptosis is frequently induced by chemotherapy. Therefore, in this study, we evaluated the capacity of an alternative type of cell death, called caspase-independent cell death, to promote proliferation.ResultsUsing a novel in vitro isogenic cellular model to trigger either apoptosis or caspase-independent cell death, we found that the later has no obvious compensatory proliferation effects on neighboring cells.ConclusionsThis study enforces the idea that alternative types of cell death such as caspase-independent cell death could be considered to replace apoptosis in the context of cancer treatment.
Highlights
Apoptosis, the most well-known type of programmed cell death, can induce in a paracrine manner a proliferative response in neighboring surviving cells called apoptosis-induced proliferation (AiP)
Setting up a cellular model to trigger apoptosis or Caspase-independent cell death (CICD) Following mitochondrial permeabilisation, cells are sentenced to certain death: when caspases are activated, this occurs within minutes through classical apoptosis and if caspase function is blocked, cells will die through CICD with a considerately slower kinetic
In order to engage CICD, caspase activation was blocked either by chemical inhibition using the pan-caspase inhibitor Q-VD-OPh or by Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated knockout of Apoptotic protease activating factor 1 (APAF-1), which is critical for caspase activation (Fig. 1a)
Summary
The most well-known type of programmed cell death, can induce in a paracrine manner a proliferative response in neighboring surviving cells called apoptosis-induced proliferation (AiP). Seminal studies performed in the 1950s revealed an odd paradigm: lethally irradiated cancer cells boost the proliferation of neighboring, healthy cells [1]. This paradoxical effect was tackled few years ago when dying cells were shown to elicit a wound healing response in neighboring cells intended to rapidly cope with tissue destruction. This so-called apoptosis-induced proliferation or AiP was described in several organisms such as flies, Hydra or Xenopus [2, 3].
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